On March 29, 2021 Checkmate Pharmaceuticals, Inc. (NASDAQ: CMPI) ("Checkmate"), a clinical stage biopharmaceutical company focused on developing its proprietary technology to harness the power of the immune system to combat cancer, reported full year 2020 financial results and provided an update on recent progress (Press release, Checkmate Pharmaceuticals, MAR 29, 2021, View Source [SID1234577267]).

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"We made strong progress in 2020, laying the groundwork to broaden and accelerate our CMP-001 clinical program in melanoma and other solid tumor indications," said Barry Labinger, President and Chief Executive Officer of Checkmate.

Recent Progress

In December 2020, Checkmate announced a clinical collaboration with Bristol Myers Squibb to evaluate vidutolimod (formerly CMP-001) in combination with nivolumab. The companies will collaborate on two melanoma clinical trials.
In January 2021, Checkmate appointed Robert F. Dolski as Chief Financial Officer. Mr. Dolski brings more than 20 years of diversified management experience as a life sciences financial executive.
Vidutolimod (formerly CMP-001) Anticipated 2021 Milestones

Advance lead melanoma indication toward potential registration, supported by two Phase 2 trials. These trials will study vidutolimod in combination with nivolumab for the treatment of anti-PD-1 refractory melanoma and first-line metastatic or unresectable melanoma. We initiated patient dosing in the first-line melanoma trial in March 2021. Trial sites have been activated and patient screening is underway in the refractory melanoma study.
Expand into new indications, such as head and neck cancer, which is expected to be supported by a Phase 2 proof-of-concept trial. This trial will study vidutolimod in combination with pembrolizumab for the treatment of first-line head and neck cancer. Trial sites have been activated and patient screening is underway. Initial data from this trial are expected before the end of 2021.
Full Year 2020 Financial Results

Cash, cash equivalents and investments: Cash, cash equivalents and investments were $125.9 million as of December 31, 2020.
Research and development expenses (R&D): R&D Expenses for the full year 2020 were $26.7 million, compared to $24.3M for the prior year. The increase was primarily attributable to increased headcount and consulting costs in connection with preparing for the initiation of planned additional clinical trials of CMP-001. These increases were partially offset by a decrease in contract manufacturing costs.
General and administration expenses (G&A): G&A expenses for the full year 2020 were $10.2 million, compared to $4.6 million for the prior year. The increase was primarily attributable to increases in personnel and other operating expenses incurred in connection with Checkmate beginning to operate as a publicly traded company.
Net loss: Net loss for the full year 2020 was $36.9 million, compared to $28.3 million for the prior year.

On March 29, 2021 Merck (NYSE: MRK), known as MSD outside the United States and Canada, reported that the U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) regarding Merck’s supplemental Biologics License Application (sBLA) seeking approval for KEYTRUDA, the company’s anti-PD-1 therapy, for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC), in combination with chemotherapy as neoadjuvant (pre-operative) treatment, then continuing as a single agent as adjuvant (post-operative) treatment after surgery (Press release, Merck & Co, MAR 29, 2021, View Source [SID1234577266]). Merck is reviewing the letter and will discuss next steps with the FDA.

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The application was based on pCR data and early interim event-free survival (EFS) findings from the Phase 3 KEYNOTE-522 trial, which is continuing to evaluate for EFS. Ahead of the Prescription Drug User Fee Act (PDUFA) action date for the application, the FDA’s Oncologic Drugs Advisory Committee voted 10-0 that a regulatory decision should be deferred until further data are available from KEYNOTE-522. The next interim analysis is calendar-driven and will occur in the third quarter of 2021.

This CRL does not impact any current approved indications for KEYTRUDA, including the indication for KEYTRUDA in combination with chemotherapy for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (Combined Positive Score [CPS] ≥10), as determined by an FDA-approved test. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

About KEYTRUDA (pembrolizumab) Injection, 100 mg

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

Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,400 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient’s likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected KEYTRUDA (pembrolizumab) Indications in the U.S.

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.

Non-Small Cell Lung Cancer

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is stage III where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

Head and Neck Squamous Cell Cancer

KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [combined positive score (CPS) ≥1] as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.

Primary Mediastinal Large B-Cell Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 (CPS ≥10), as determined by an FDA-approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.

Microsatellite Instability-High or Mismatch Repair Deficient Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)

solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options, or
colorectal cancer that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan.
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.

Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer

KEYTRUDA is indicated for the first-line treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC).

Gastric Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Esophageal Cancer

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either:

in combination with platinum- and fluoropyrimidine-based chemotherapy, or
as a single agent after one or more prior lines of systemic therapy for patients with tumors of squamous cell histology that express PD L1 (CPS ≥10) as determined by an FDA approved test
Cervical Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Hepatocellular Carcinoma

KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Merkel Cell Carcinoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Renal Cell Carcinoma

KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

Tumor Mutational Burden-High

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.

Cutaneous Squamous Cell Carcinoma

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) that is not curable by surgery or radiation.

Triple-Negative Breast Cancer

KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Selected Important Safety Information for KEYTRUDA

Severe and Fatal Immune-Mediated Adverse Reactions

KEYTRUDA is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death receptor-1 (PD-1) or the programmed death ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, can affect more than one body system simultaneously, and can occur at any time after starting treatment or after discontinuation of treatment. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions.

Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Early identification and management are essential to ensure safe use of anti–PD-1/PD-L1 treatments. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue KEYTRUDA depending on severity of the immune-mediated adverse reaction. In general, if KEYTRUDA requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose adverse reactions are not controlled with corticosteroid therapy.

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis. The incidence is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 3.4% (94/2799) of patients receiving KEYTRUDA, including fatal (0.1%), Grade 4 (0.3%), Grade 3 (0.9%), and Grade 2 (1.3%) reactions. Systemic corticosteroids were required in 67% (63/94) of patients. Pneumonitis led to permanent discontinuation of KEYTRUDA in 1.3% (36) and withholding in 0.9% (26) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Pneumonitis resolved in 59% of the 94 patients.

Pneumonitis occurred in 8% (31/389) of adult patients with cHL receiving KEYTRUDA as a single agent, including Grades 3-4 in 2.3% of patients. Patients received high-dose corticosteroids for a median duration of 10 days (range: 2 days to 53 months). Pneumonitis rates were similar in patients with and without prior thoracic radiation. Pneumonitis led to discontinuation of KEYTRUDA in 5.4% (21) of patients. Of the patients who developed pneumonitis, 42% of these patients interrupted KEYTRUDA, 68% discontinued KEYTRUDA, and 77% had resolution.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis, which may present with diarrhea. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (1.1%), and Grade 2 (0.4%) reactions. Systemic corticosteroids were required in 69% (33/48); additional immunosuppressant therapy was required in 4.2% of patients. Colitis led to permanent discontinuation of KEYTRUDA in 0.5% (15) and withholding in 0.5% (13) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Colitis resolved in 85% of the 48 patients.

Hepatotoxicity and Immune-Mediated Hepatitis

KEYTRUDA as a Single Agent

KEYTRUDA can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.4%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 68% (13/19) of patients; additional immunosuppressant therapy was required in 11% of patients. Hepatitis led to permanent discontinuation of KEYTRUDA in 0.2% (6) and withholding in 0.3% (9) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, none had recurrence. Hepatitis resolved in 79% of the 19 patients.

KEYTRUDA with Axitinib

KEYTRUDA in combination with axitinib can cause hepatic toxicity. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider monitoring more frequently as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased alanine aminotransferase (ALT) (20%) and increased aspartate aminotransferase (AST) (13%) were seen, which was at a higher frequency compared to KEYTRUDA alone. Fifty-nine percent of the patients with increased ALT received systemic corticosteroids. In patients with ALT ≥3 times upper limit of normal (ULN) (Grades 2-4, n=116), ALT resolved to Grades 0-1 in 94%. Among the 92 patients who were rechallenged with either KEYTRUDA (n=3) or axitinib (n=34) administered as a single agent or with both (n=55), recurrence of ALT ≥3 times ULN was observed in 1 patient receiving KEYTRUDA, 16 patients receiving axitinib, and 24 patients receiving both. All patients with a recurrence of ALT ≥3 ULN subsequently recovered from the event.

Immune-Mediated Endocrinopathies

Adrenal Insufficiency

KEYTRUDA can cause primary or secondary adrenal insufficiency. For Grade 2 or higher, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold KEYTRUDA depending on severity. Adrenal insufficiency occurred in 0.8% (22/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.3%) reactions. Systemic corticosteroids were required in 77% (17/22) of patients; of these, the majority remained on systemic corticosteroids. Adrenal insufficiency led to permanent discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.3% (8) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Hypophysitis

KEYTRUDA can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Hypophysitis occurred in 0.6% (17/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.2%) reactions. Systemic corticosteroids were required in 94% (16/17) of patients; of these, the majority remained on systemic corticosteroids. Hypophysitis led to permanent discontinuation of KEYTRUDA in 0.1% (4) and withholding in 0.3% (7) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Thyroid Disorders

KEYTRUDA can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Thyroiditis occurred in 0.6% (16/2799) of patients receiving KEYTRUDA, including Grade 2 (0.3%). None discontinued, but KEYTRUDA was withheld in <0.1% (1) of patients.

Hyperthyroidism occurred in 3.4% (96/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (0.8%). It led to permanent discontinuation of KEYTRUDA in <0.1% (2) and withholding in 0.3% (7) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement. Hypothyroidism occurred in 8% (237/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (6.2%). It led to permanent discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.5% (14) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement. The majority of patients with hypothyroidism required long-term thyroid hormone replacement. The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC, occurring in 16% of patients receiving KEYTRUDA as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. The incidence of new or worsening hypothyroidism was higher in 389 adult patients with cHL (17%) receiving KEYTRUDA as a single agent, including Grade 1 (6.2%) and Grade 2 (10.8%) hypothyroidism.

Type 1 Diabetes Mellitus (DM), Which Can Present With Diabetic Ketoacidosis

Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold KEYTRUDA depending on severity. Type 1 DM occurred in 0.2% (6/2799) of patients receiving KEYTRUDA. It led to permanent discontinuation in <0.1% (1) and withholding of KEYTRUDA in <0.1% (1). All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Immune-Mediated Nephritis With Renal Dysfunction

KEYTRUDA can cause immune-mediated nephritis. Immune-mediated nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.1%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 89% (8/9) of patients. Nephritis led to permanent discontinuation of KEYTRUDA in 0.1% (3) and withholding in 0.1% (3) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, none had recurrence. Nephritis resolved in 56% of the 9 patients.

Immune-Mediated Dermatologic Adverse Reactions

KEYTRUDA can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms, and toxic epidermal necrolysis, has occurred with anti–PD-1/PD-L1 treatments. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes. Withhold or permanently discontinue KEYTRUDA depending on severity. Immune-mediated dermatologic adverse reactions occurred in 1.4% (38/2799) of patients receiving KEYTRUDA, including Grade 3 (1%) and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 40% (15/38) of patients. These reactions led to permanent discontinuation in 0.1% (2) and withholding of KEYTRUDA in 0.6% (16) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 6% had recurrence. The reactions resolved in 79% of the 38 patients.

Other Immune-Mediated Adverse Reactions

The following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% (unless otherwise noted) in patients who received KEYTRUDA or were reported with the use of other anti–PD-1/PD-L1 treatments. Severe or fatal cases have been reported for some of these adverse reactions. Cardiac/Vascular: Myocarditis, pericarditis, vasculitis; Nervous System: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy; Ocular: Uveitis, iritis and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss; Gastrointestinal: Pancreatitis, to include increases in serum amylase and lipase levels, gastritis, duodenitis; Musculoskeletal and Connective Tissue: Myositis/polymyositis rhabdomyolysis (and associated sequelae, including renal failure), arthritis (1.5%), polymyalgia rheumatica; Endocrine: Hypoparathyroidism; Hematologic/Immune: Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection.

Infusion-Related Reactions

KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 0.2% of 2799 patients receiving KEYTRUDA. Monitor for signs and symptoms of infusion-related reactions. Interrupt or slow the rate of infusion for Grade 1 or Grade 2 reactions. For Grade 3 or Grade 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after anti–PD-1/PD-L1 treatment. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute and chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between anti–PD-1/PD-L1 treatment and allogeneic HSCT. Follow patients closely for evidence of these complications and intervene promptly. Consider the benefit vs risks of using anti–PD-1/PD-L1 treatments prior to or after an allogeneic HSCT.

Increased Mortality in Patients With Multiple Myeloma

In trials in patients with multiple myeloma, the addition of KEYTRUDA to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of these patients with an anti–PD-1/PD-L1 treatment in this combination is not recommended outside of controlled trials.

Embryofetal Toxicity

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. Advise women of this potential risk. In females of reproductive potential, verify pregnancy status prior to initiating KEYTRUDA and advise them to use effective contraception during treatment and for 4 months after the last dose.

Adverse Reactions

In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to permanent discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). The most common adverse reactions (≥20%) with KEYTRUDA were fatigue (28%), diarrhea (26%), rash (24%), and nausea (21%).

In KEYNOTE-054, KEYTRUDA was permanently discontinued due to adverse reactions in 14% of 509 patients; the most common (≥1%) were pneumonitis (1.4%), colitis (1.2%), and diarrhea (1%). Serious adverse reactions occurred in 25% of patients receiving KEYTRUDA. The most common adverse reaction (≥20%) with KEYTRUDA was diarrhea (28%).

In KEYNOTE-189, when KEYTRUDA was administered with pemetrexed and platinum chemotherapy in metastatic nonsquamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 20% of 405 patients. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonitis (3%) and acute kidney injury (2%). The most common adverse reactions (≥20%) with KEYTRUDA were nausea (56%), fatigue (56%), constipation (35%), diarrhea (31%), decreased appetite (28%), rash (25%), vomiting (24%), cough (21%), dyspnea (21%), and pyrexia (20%).

In KEYNOTE-407, when KEYTRUDA was administered with carboplatin and either paclitaxel or paclitaxel protein-bound in metastatic squamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 15% of 101 patients. The most frequent serious adverse reactions reported in at least 2% of patients were febrile neutropenia, pneumonia, and urinary tract infection. Adverse reactions observed in KEYNOTE-407 were similar to those observed in KEYNOTE-189 with the exception that increased incidences of alopecia (47% vs 36%) and peripheral neuropathy (31% vs 25%) were observed in the KEYTRUDA and chemotherapy arm compared to the placebo and chemotherapy arm in KEYNOTE-407.

In KEYNOTE-042, KEYTRUDA was discontinued due to adverse reactions in 19% of 636 patients with advanced NSCLC; the most common were pneumonitis (3%), death due to unknown cause (1.6%), and pneumonia (1.4%). The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia (7%), pneumonitis (3.9%), pulmonary embolism (2.4%), and pleural effusion (2.2%). The most common adverse reaction (≥20%) was fatigue (25%).

In KEYNOTE-010, KEYTRUDA monotherapy was discontinued due to adverse reactions in 8% of 682 patients with metastatic NSCLC; the most common was pneumonitis (1.8%). The most common adverse reactions (≥20%) were decreased appetite (25%), fatigue (25%), dyspnea (23%), and nausea (20%).

In KEYNOTE-048, KEYTRUDA monotherapy was discontinued due to adverse events in 12% of 300 patients with HNSCC; the most common adverse reactions leading to permanent discontinuation were sepsis (1.7%) and pneumonia (1.3%). The most common adverse reactions (≥20%) were fatigue (33%), constipation (20%), and rash (20%).

In KEYNOTE-048, when KEYTRUDA was administered in combination with platinum (cisplatin or carboplatin) and FU chemotherapy, KEYTRUDA was discontinued due to adverse reactions in 16% of 276 patients with HNSCC. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonia (2.5%), pneumonitis (1.8%), and septic shock (1.4%). The most common adverse reactions (≥20%) were nausea (51%), fatigue (49%), constipation (37%), vomiting (32%), mucosal inflammation (31%), diarrhea (29%), decreased appetite (29%), stomatitis (26%), and cough (22%).

In KEYNOTE-012, KEYTRUDA was discontinued due to adverse reactions in 17% of 192 patients with HNSCC. Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. The most common adverse reactions (≥20%) were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were generally similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy, with the exception of increased incidences of facial edema and new or worsening hypothyroidism.

In KEYNOTE-204, KEYTRUDA was discontinued due to adverse reactions in 14% of 148 patients with cHL. Serious adverse reactions occurred in 30% of patients receiving KEYTRUDA; those ≥1% were pneumonitis, pneumonia, pyrexia, myocarditis, acute kidney injury, febrile neutropenia, and sepsis. Three patients died from causes other than disease progression: 2 from complications after allogeneic HSCT and 1 from unknown cause. The most common adverse reactions (≥20%) were upper respiratory tract infection (41%), musculoskeletal pain (32%), diarrhea (22%), and pyrexia, fatigue, rash, and cough (20% each).

In KEYNOTE-087, KEYTRUDA was discontinued due to adverse reactions in 5% of 210 patients with cHL. Serious adverse reactions occurred in 16% of patients; those ≥1% were pneumonia, pneumonitis, pyrexia, dyspnea, GVHD, and herpes zoster. Two patients died from causes other than disease progression: 1 from GVHD after subsequent allogeneic HSCT and 1 from septic shock. The most common adverse reactions (≥20%) were fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%), and rash (20%).

In KEYNOTE-170, KEYTRUDA was discontinued due to adverse reactions in 8% of 53 patients with PMBCL. Serious adverse reactions occurred in 26% of patients and included arrhythmia (4%), cardiac tamponade (2%), myocardial infarction (2%), pericardial effusion (2%), and pericarditis (2%). Six (11%) patients died within 30 days of start of treatment. The most common adverse reactions (≥20%) were musculoskeletal pain (30%), upper respiratory tract infection and pyrexia (28% each), cough (26%), fatigue (23%), and dyspnea (21%).

In KEYNOTE-052, KEYTRUDA was discontinued due to adverse reactions in 11% of 370 patients with locally advanced or metastatic urothelial carcinoma. Serious adverse reactions occurred in 42% of patients; those ≥2% were urinary tract infection, hematuria, acute kidney injury, pneumonia, and urosepsis. The most common adverse reactions (≥20%) were fatigue (38%), musculoskeletal pain (24%), decreased appetite (22%), constipation (21%), rash (21%), and diarrhea (20%).

In KEYNOTE-045, KEYTRUDA was discontinued due to adverse reactions in 8% of 266 patients with locally advanced or metastatic urothelial carcinoma. The most common adverse reaction resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.9%). Serious adverse reactions occurred in 39% of KEYTRUDA-treated patients; those ≥2% were urinary tract infection, pneumonia, anemia, and pneumonitis. The most common adverse reactions (≥20%) in patients who received KEYTRUDA were fatigue (38%), musculoskeletal pain (32%), pruritus (23%), decreased appetite (21%), nausea (21%), and rash (20%).

In KEYNOTE-057, KEYTRUDA was discontinued due to adverse reactions in 11% of 148 patients with high-risk NMIBC. The most common adverse reaction resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.4%). Serious adverse reactions occurred in 28% of patients; those ≥2% were pneumonia (3%), cardiac ischemia (2%), colitis (2%), pulmonary embolism (2%), sepsis (2%), and urinary tract infection (2%). The most common adverse reactions (≥20%) were fatigue (29%), diarrhea (24%), and rash (24%).

Adverse reactions occurring in patients with MSI-H or dMMR CRC were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy.

Adverse reactions occurring in patients with gastric cancer were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy.

In KEYNOTE-590, when KEYTRUDA was administered with cisplatin and fluorouracil to patients with metastatic or locally advanced esophageal or GEJ (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma who were not candidates for surgical resection or definitive chemoradiation, KEYTRUDA was discontinued due to adverse reactions in 15% of 370 patients. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA (≥1%) were pneumonitis (1.6%), acute kidney injury (1.1%), and pneumonia (1.1%). The most common adverse reactions (≥20%) with KEYTRUDA in combination with chemotherapy were nausea (67%), fatigue (57%), decreased appetite (44%), constipation (40%), diarrhea (36%), vomiting (34%), stomatitis (27%), and weight loss (24%).

Adverse reactions occurring in patients with esophageal cancer who received KEYTRUDA as a monotherapy were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy.

In KEYNOTE-158, KEYTRUDA was discontinued due to adverse reactions in 8% of 98 patients with recurrent or metastatic cervical cancer. Serious adverse reactions occurred in 39% of patients receiving KEYTRUDA; the most frequent included anemia (7%), fistula, hemorrhage, and infections [except urinary tract infections] (4.1% each). The most common adverse reactions (≥20%) were fatigue (43%), musculoskeletal pain (27%), diarrhea (23%), pain and abdominal pain (22% each), and decreased appetite (21%).

Adverse reactions occurring in patients with hepatocellular carcinoma (HCC) were generally similar to those in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy, with the exception of increased incidences of ascites (8% Grades 3-4) and immune-mediated hepatitis (2.9%). Laboratory abnormalities (Grades 3-4) that occurred at a higher incidence were elevated AST (20%), ALT (9%), and hyperbilirubinemia (10%).

Among the 50 patients with MCC enrolled in study KEYNOTE-017, adverse reactions occurring in patients with MCC were generally similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy. Laboratory abnormalities (Grades 3-4) that occurred at a higher incidence were elevated AST (11%) and hyperglycemia (19%).

In KEYNOTE-426, when KEYTRUDA was administered in combination with axitinib, fatal adverse reactions occurred in 3.3% of 429 patients. Serious adverse reactions occurred in 40% of patients, the most frequent (≥1%) were hepatotoxicity (7%), diarrhea (4.2%), acute kidney injury (2.3%), dehydration (1%), and pneumonitis (1%). Permanent discontinuation due to an adverse reaction occurred in 31% of patients; KEYTRUDA only (13%), axitinib only (13%), and the combination (8%); the most common were hepatotoxicity (13%), diarrhea/colitis (1.9%), acute kidney injury (1.6%), and cerebrovascular accident (1.2%). The most common adverse reactions (≥20%) were diarrhea (56%), fatigue/asthenia (52%), hypertension (48%), hepatotoxicity (39%), hypothyroidism (35%), decreased appetite (30%), palmar-plantar erythrodysesthesia (28%), nausea (28%), stomatitis/mucosal inflammation (27%), dysphonia (25%), rash (25%), cough (21%), and constipation (21%).

Adverse reactions occurring in patients with TMB-H cancer were similar to those occurring in patients with other solid tumors who received KEYTRUDA as a single agent.

Adverse reactions occurring in patients with cSCC were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy.

In KEYNOTE-355, when KEYTRUDA and chemotherapy (paclitaxel, paclitaxel protein-bound, or gemcitabine and carboplatin) were administered to patients with locally recurrent unresectable or metastatic TNBC (n=596) who had not been previously treated with chemotherapy in the metastatic setting, fatal adverse reactions occurred in 2.5% of patients, including cardio-respiratory arrest (0.7%) and septic shock (0.3%). Serious adverse reactions occurred in 30% of patients receiving KEYTRUDA in combination with chemotherapy, the most common were: pneumonia (2.9%), anemia (2.2%), and thrombocytopenia (2%). KEYTRUDA was discontinued in 11% of patients due to adverse reactions. The most common adverse reactions resulting in permanent discontinuation (≥1%) were increased ALT (2.2%), increased AST (1.5%), and pneumonitis (1.2%). The most common adverse reactions (≥20%) in patients receiving KEYTRUDA in combination with chemotherapy were: fatigue (48%), nausea (44%), alopecia (34%), diarrhea and constipation (28% each), vomiting and rash (26% each), cough (23%), decreased appetite (21%), and headache (20%).

Lactation

Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for 4 months after the final dose.

Pediatric Use

In KEYNOTE-051, 161 pediatric patients (62 pediatric patients aged 6 months to younger than 12 years and 99 pediatric patients aged 12 years to 17 years) were administered KEYTRUDA 2 mg/kg every 3 weeks. The median duration of exposure was 2.1 months (range: 1 day to 24 months).

Adverse reactions that occurred at a ≥10% higher rate in pediatric patients when compared to adults were pyrexia (33%), vomiting (30%), leukopenia (30%), upper respiratory tract infection (29%), neutropenia (26%), headache (25%), and Grade 3 anemia (17%).

Merck’s Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

About the Merck Access Program for KEYTRUDA

At Merck, we are committed to supporting accessibility to our cancer medicines. Merck provides multiple programs to help appropriate patients who are prescribed KEYTRUDA have access to our anti-PD-1 therapy. The Merck Access Program provides reimbursement support for patients receiving KEYTRUDA, including information to help with out-of-pocket costs and co-pay assistance for eligible patients. More information is available by calling 855-257-3932 or visiting www.merckaccessprogram-keytruda.com.

About Merck’s Patient Support Program for KEYTRUDA

Merck is committed to helping provide patients and their caregivers support throughout their treatment with KEYTRUDA. The KEY+YOU Patient Support Program provides a range of resources and support. For further information and to sign up, eligible patients may call 85-KEYTRUDA (855-398-7832) or visit www.keytruda.com.

On March 29, 2021 Decibel Therapeutics (Nasdaq: DBTX), a clinical-stage biotechnology company dedicated to discovering and developing transformative treatments to restore and improve hearing and balance, reported financial results for the fourth quarter and full year ended December 31, 2020 and provided a corporate update (Press release, Decibel Therapeutics, MAR 29, 2021, View Source [SID1234577265]).

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"The past nine months have been a strong period of execution for Decibel as we accomplished several key milestones. The closing of two upsized financings – our Series D and IPO – as well as an important partnership with Catalent focused on development and manufacturing of our lead gene therapy program for hearing loss, DB-OTO, place Decibel in a strong position operationally and financially to execute on our goals for 2021," said Laurence Reid, Ph.D., Chief Executive Officer of Decibel. "Across our pipeline, we expect to announce important advances throughout this year. We look forward to further leveraging our proprietary platform of integrated single-cell genomics and bioinformatics analyses applied to the inner ear, as we advance our precision gene therapy pipeline for hearing and balance disorders."

Company Highlights:

Advanced DB-OTO for otoferlin (OTOF) -related hearing loss; on track for IND submission and Phase 1/2 clinical trial initiation in 2022.

Signed New Development and Manufacturing Agreement for Dual-Vector Gene Therapy with Catalent: In February 2021, Decibel announced a new agreement with Catalent to provide Decibel with process and analytical development, as well as cGMP manufacturing services for its lead gene therapy product candidate, DB-OTO, being developed for individuals with hearing loss due to mutation of the OTOF gene.

Announced Exclusive Licensing Agreements for Hearing Gene Therapy Technology with the University of Florida and the University of California, San Francisco: In November 2020, Decibel announced two exclusive license agreements for an adeno-associated virus (AAV) gene therapy technology designed to restore hearing to individuals with profound, congenital hearing loss caused by mutations in the otoferlin gene.

Launched Amplify Genetic Testing Program with Invitae: In December 2020, Decibel launched Amplify, a no-charge genetic testing program to screen for the genetic cause of congenital hearing loss in children diagnosed with auditory neuropathy with the genetic testing company, Invitae.

Presented New Preclinical Data at the 44th Annual Association for Research in Otolaryngology Conference (ARO): In February 2021, Decibel presented preclinical findings supporting the Company’s lead gene therapy product candidate, DB-OTO. The presentations included data from studies in non-human primates of the surgical approach for DB-OTO in which dual vector AAV and Decibel’s cell-selective promoter drove highly selective expression of GFP in hair cells of non-human primates which demonstrated successful distribution and expression across the cochlear length in non-human primates. Additionally, the Company presented findings from preclinical studies of DB-OTO in mice and non-human primates in which hair cell-selective expression of OTOF enabled efficacy and durability and minimized potential toxicity.

Received U.S. Food and Drug Administration (FDA) Fast Track Designation for DB-020: In December 2020, Decibel announced that its clinical product candidate for the prevention of cisplatin-induced hearing loss, DB-020, was granted Fast Track designation by the U.S. FDA.
Corporate Highlights:

Closed Upsized Initial Public Offering: In February 2021, Decibel completed its Initial Public Offering of 7,662,000 shares of common stock at a public offering price of $18.00 per share. Net proceeds from the offering, after deducting underwriting discounts and offering expenses, were approximately $124.8 million.

Closed $82.2M Series D Financing: In November 2020, Decibel announced the closing of its oversubscribed Series D financing, which raised proceeds of $82.2 million. The financing was led by OrbiMed with new investments from BlackRock Health Sciences, Casdin Capital, Janus Henderson, Samsara BioCapital and Surveyor Capital, along with existing investor participation from Foresite Capital, GV, S-Cubed, Sobrato Capital, SR One and Third Rock Ventures.

Strengthened Board of Directors with Appointment of Peter A. Thompson, M.D., F.A.C.P.: In November 2020, Decibel announced the appointment of Peter. A. Thompson, M.D., F.A.C.P., to its board of directors. Dr. Thompson is currently a partner at OrbiMed.

Added to Russell 2000 Index: Effective March 22, 2021, Decibel was added to the Russell 2000 Index as part of its quarterly IPO additions. The Russell 2000 Index is a subset of the Russell 3000 Index, which measures the performance of the small-cap segment of the U.S. equity market.
Fourth Quarter and Full Year 2020 Financial Results:

Cash Position: As of December 31, 2020, cash, cash equivalents and available-for-sale securities were $54.3 million, compared to $32.3 million as of December 31, 2019. The increase in cash, cash equivalents and available-for-sale securities was primarily due to closing the initial tranche of the Series D financing in November 2020.

Research and Development Expenses: Research and development expenses were $7.9 million for the fourth quarter of 2020, compared to $3.2 million for the same period in 2019. Research and development expenses were $25.3 million for the full year 2020, compared to $29.4 million for the full year 2019. The decrease in research and development expenses for the full year 2020 was primarily due to a decrease in expenses incurred to advance the Company’s DB-020 program related to slower enrollment due to COVID-19 and a decrease in other indirect research and development expenses.

General and Administrative Expenses: General and administrative expenses were $5.1 million for the fourth quarter of 2020, compared to $3.3 million for the same period in 2019. General and administrative expenses were $14.2 million for the full year 2020, compared to $14.7 million for the full year 2019. The decrease in general and administrative expenses for the full year 2020 was primarily attributable to a decrease in facilities and personnel-related expenses due to reduced headcount partially offset by an increase in professional fees.
Financial Guidance:

Based on its current operating and development plans, Decibel believes that its existing cash, cash equivalents and available-for-sale securities will fund its pipeline programs and operating expenses into 2024.

On March 29, 2021 Silverback Therapeutics, Inc. (Nasdaq: SBTX) ("Silverback"), a clinical-stage biopharmaceutical company leveraging its proprietary ImmunoTAC technology platform to develop systemically delivered, tissue targeted therapeutics for the treatment of cancer, chronic viral infections, and other serious diseases, reported financial results and provided a corporate update for the fourth quarter and full year ended December 31, 2020 (Press release, Silverback Therapeutics, MAR 29, 2021, View Source [SID1234577264]).

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"2020 was an extraordinary year for Silverback, with the initiation of our first clinical study for SBT6050, in which pharmacological activity was observed in the first dose cohort, the advancement of each of our preclinical programs, expansion of our strong team, and the successful closing of our IPO in December," said Laura Shawver, Ph.D., chief executive officer of Silverback. "We are well-positioned to execute on our mission to develop a new class of tissue-localized therapies that are designed to modulate fundamental biological pathways in cancer and beyond."

2020 Corporate Highlights and 2021 Anticipated Milestones

SBT6050 (HER2-TLR8 ImmunoTAC) Phase 1/1b clinical study initiated, with pharmacological activity demonstrated in the first dose cohort. SBT6050 is being studied as a monotherapy and in combination with pembrolizumab, in patients with advanced or metastatic HER2-expressing solid tumors. Changes in pharmacodynamic markers consistent with the potential mechanism of action have been observed in patients treated in the first monotherapy dose cohort. Enrollment is ongoing in Part 1 of the study (SBT6050 monotherapy dose escalation) and treatment has been initiated in Part 3 of the study (SBT6050 plus pembrolizumab dose-escalation). Silverback is on track to deliver interim clinical data from Part 1 of the study in the second half of 2021.
SBT6290 (Nectin4-TLR8 ImmunoTAC) continues to advance through preclinical development. SBT6290 includes the same TLR8 agonist linker-payload used in SBT6050, conjugated to a proprietary Nectin4-directed monoclonal antibody. Pre-Investigational New Drug (IND) alignment with the FDA was achieved in February 2021 and an IND application is expected in the fourth quarter of 2021. The initiation of a Phase 1/1b clinical study is anticipated in the first quarter of 2022.
SBT8230 (ASGR1-TLR8 ImmunoTAC) development candidate selected in the fourth quarter of 2020. SBT8230 includes the same TLR8 agonist linker-payload used in SBT6050, conjugated to a proprietary ASGR1-directed monoclonal antibody, and is designed to activate human myeloid cells in the liver for treatment of chronic hepatitis B viral infection. CMC scale up and preclinical work continues with IND-enabling toxicology studies expected to commence in the first quarter of 2022.
Completed initial public offering resulting in $277.7 million in gross proceeds. Silverback completed an IPO in December 2020, selling 13,225,000 shares at a public offering price of $21.00 per share, raising gross proceeds of $277.7 million (before deducting underwriting discounts and commissions and offering costs). In September 2020, the Company completed a Series C financing, raising $85.0 million in gross proceeds, and in March, July and September 2020, completed a Series B financing, raising $78.5 million in gross proceeds (including $10.1 million upon the conversion of then outstanding convertible notes and accrued interest thereon).
Financial Results

For the fourth quarter ended December 31, 2020, Silverback reported a net loss of $13.1 million, compared to a net loss of $7.0 million for the comparable period in 2019. For the year ended December 31, 2020, the Company reported a net loss of $32.9 million, compared to a net loss of $24.0 million for 2019. Net loss for the fourth quarter and full year of 2020 included non-cash stock-based compensation expense of $2.3 million and $2.6 million, respectively, compared to $42,000 and $148,000 for the same periods in 2019, respectively.

Research and development expenses for the fourth quarter ended December 31, 2020 were $8.8 million, compared to $6.3 million for the same period in 2019. For the year ended December 31, 2020, research and development expenses were $24.6 million, compared to $21.5 million for 2019. The increases in the Company’s research and development expenses for the 2020 periods, as compared to the same periods in 2019, were primarily attributable to the advancement of pipeline programs, including SBT6290 and SBT8230, into preclinical development. Silverback also incurred additional personnel-related expenses in 2020 as compared to 2019 as operations grew in support of program advances. These increases were partially offset by a decrease in expenses related to the development of SBT6050 as the program completed manufacturing activities and initiated a Phase 1/1b clinical trial in the second half of 2020.

General and administrative expenses for the fourth quarter ended December 31, 2020 were $4.3 million, compared to $0.7 million for the same period in 2019. For the year ended December 31, 2020, general and administrative expenses were $8.3 million, compared to $2.6 million for the same period in 2019. The increases in general and administrative expenses for the 2020 periods, as compared to the same periods in 2019, were primarily attributable to an increase in personnel-related expenses due to increased headcount in 2020, including new executives, as well as increases in salaries, bonuses, and stock-based compensation. The increase in general and administrative expenses was also due to an increase in legal fees, professional fees, and other various general and administrative expenses as we prepared to become a public company.

As of December 31, 2020, Silverback reported cash and cash equivalents of $386.6 million, compared to $10.0 million at December 31, 2019, which is expected to fund operating expenses and capital expenditure requirements for at least the next 24 months. The Company’s cash and cash equivalents balance at December 31, 2020 included $255.3 million of proceeds, net of offering costs, from the Company’s initial public offering in December 2020, and $153.3 million of proceeds, net of offering costs, from the Company’s Series B and Series C financings in 2020. As of December 31, 2020, the Company had 34,801,537 common shares outstanding.

On March 29, 2021 I-Mab (the "Company") (Nasdaq: IMAB), a clinical stage biopharmaceutical company committed to the discovery, development and commercialization of novel biologics, reported financial results for the full year ended December 31, 2020 and provided key business updates (Press release, I-Mab Biopharma, MAR 29, 2021, View Source [SID1234577263]).

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"In an unprecedented year marked by the global pandemic, I-Mab outperformed in delivering outstanding results to accelerate our progress towards becoming a fully-integrated global biopharma company," said Dr. Jingwu Zang, Founder, Chairman and Director of I-Mab. "We have accomplished 18 significant clinical milestones since our IPO last year and our pipeline today has advanced to include three registrational trials with the first NDA planned later this year for a total 19 clinical trials either on-going or to be initiated in both the United States and China."

I-Mab’s globally competitive pipeline has now progressed to include 16 novel or highly differentiated assets with 11 in clinical development stages and five in the pre-clinical stage. The Company’s pre-NDA and core clinical assets of near-term value realization, including felzartamab (TJ202) and eftansomatropin alfa (TJ101), are progressing towards NDA. In addition, two highly differentiated investigational drugs, lemzoparlimab (TJC4) and uliledlimab (TJD5), have achieved critical progress as global front-runners. I-Mab’s next wave of innovative assets, epitomized by the novel bispecific antibodies TJ-L14B and TJ-CD4B, are now moving into clinical trials in the U.S.

In the near-term, I-Mab will continue creating corporate value by delivering on a series of critical milestones including the planned NDA submission for felzartamab in 2021 as well as forging potential strategic global out-licensing partnerships for uliledlimab and other innovative assets and selected in-licensing partnerships to enrich its pipeline. The focused R&D effort is further complemented by the Company’s new discovery initiative to create the next generation of innovative assets through transformative platform technologies.

"We are confident in our innovative R&D strength in immuno-oncology to continue advancing and upgrading our globally competitive pipeline." Dr. Zang concluded.

In addition to creating the near-term value, the Company has also made notable strides in its journey to become a global biopharmaceutical company, which include building a state-of-the-art GMP manufacturing facility in China with a pilot plant and commercial scale production lines.

In parallel, I-Mab has begun to execute a commercialization plan that focuses on building a leading position in hematologic oncology in China, leveraging I-Mab’s core assets (i.e., felzartamab and lemzoparlimab) and additional key product(s) to be in-licensed. As both assets are progressing towards NDA, preparations are being made for product launch and commercialization. Our revenue stream generated from out-licensing deals grew tremendously in 2020 to make I-Mab profitable for the first time and is expected to converge with product sales revenues to be generated in a near term, projecting a promising financial outlook for the Company and its shareholders.

Overview of Operations

I-Mab currently has three registrational trials underway, 16 phase 1 and 2 clinical studies – either ongoing or to be initiated soon in both the U.S. and China – and five on-going pre-clinical programs in 2021. Four additional new discovery programs are set to advance to the pre-clinical development stage by the end of 2021 as a result of the new discovery initiative.

I-Mab has achieved critical advancements in core clinical assets in early 2021. These achievements include the full patient enrollment for felzartamab in the third-line multiple myeloma trial, a key step for the NDA submission that is on track for late 2021, and the initiation to enroll patients for the registrational clinical trial of eftansomatropin alfa. The Company has also set forth with its accelerated clinical development plan for lemzoparlimab, aiming for NDA approval as the first CD47 antibody drug for the treatment of hematologic malignancies (such as MDS, AML and NHL) in China while continuing to advance clinical trials in solid tumors in combination with PD-1 therapy.

These clinical trials are on-going in the U.S. and China with preliminary data readouts planned in Q4 2021 for the non-Hodgkin’s lymphoma (NHL) study and the solid tumor study in the U.S. The Company also plans to initiate a combination clinical trial of lemzoparlimab with felzartamab as a possible novel treatment option for relapsed and refractory and newly diagnosed MM with a potential to become first-line treatment if proven in addition to felzartamab currently being evaluated as a second-line and third-line treatment for MM.

For uliledlimab, a globally competitive and differentiated CD73 antibody, the Company recently completed a phase 1 clinical study in the U.S., which demonstrated favorable safety, PK/PD and receptor occupancy profile, together with observed clinical activity of the investigational drug in cancer patients. The detailed clinical data have been submitted for presentation at ASCO (Free ASCO Whitepaper) 2021. In addition, a combined phase 1/2 clinical trial has been ongoing and the dose expansion part of the trial will be initiated in combination with PD-1 therapy in patients with cancers in China in 2H 2021.

Already operating globally with five hubs in China and the U.S., I-Mab has plans to open a new R&D center in San Diego, CA, focusing on translational medicine and formulation research. In preparation for the market launch of its initial series of products in China, the Company is in construction of a comprehensive biologics manufacturing facility in Hangzhou, China, and is building up its commercialization capabilities.

To support its long-term growth, I-Mab is actively monitoring market conditions and considering potential options for further equity listings on Greater China stock exchanges such as the STAR Market in Shanghai and the Main Board of the Hong Kong Stock Exchange under Chapter 18A of the Hong Kong Listing Rules.

Recent Pipeline Highlights and Upcoming Milestones

Core Clinical Assets – Global Frontrunners

Lemzoparlimab (TJC4): A highly differentiated CD47 antibody being developed for oncology indications. The results of the US phase 1 clinical trial in patients with solid tumor indicate potential clinical advantages of lemzoparlimab in safety and PK with observed clinical activity, which does not require priming dose as compared to other clinical stage CD47 antibodies. Lemzoparlimab is being developed through a comprehensive clinical development plan for hematologic oncology and solid tumor in global collaboration with AbbVie.

Global Collaboration with AbbVie: In September 2020, to facilitate and accelerate the global development and commercialization of lemzoparlimab, I-Mab granted AbbVie a global license valued at US$1.94 billion, including an upfront payment of US$180 million and the first milestone payment of US$20 million based on the phase 1 clinical results. I-Mab retains the rights to develop and commercialize lemzoparlimab in Mainland China, Hong Kong and Macau. We believe that this global collaboration with AbbVie will greatly facilitate the clinical development, manufacturing and commercialization of lemzoparlimab globally and in China.

Hematologic malignancies: Our prioritized development goal is to achieve an accelerated approval of lemzoparlimab in China, ideally as the first CD47 antibody product in China. MDS and possibly NHL are being considered as potential first indication(s) as they hold the high probability of success for accelerated approvals.

(1) With the approved IND, the Company is initiating an abbreviated phase 2 clinical study of lemzoparlimab in combination with AZA in patients with AML and MDS, potentially bridging the clinical study – pending approval by the National Medical Products Administration (NMPA) – to a registrational clinical trial in patients with MDS.

(2) The Company continues to enroll more patients with NHL in a combination clinical trial with rituximab (Rituxan) in the U.S. This clinical trial includes clinical sites in China through an IMCT (international multi-center trial) mechanism in order to potentially bridge – pending approval by the NMPA – to a registrational clinical trial in NHL in China. The preliminary data readout of the NHL trial is set in Q4 2021.

(3) The Company will participate in a global clinical trial to be led by AbbVie in patients with AML for registrational purposes globally by AbbVie and in China by I-Mab.
Solid tumor indications: The Company will continue advancing the current cohort expansion study in the U.S., combining lemzoparlimab with pembrolizumab (Keytruda) to evaluate the safety and efficacy in patients with NSCLC and ovarian cancer. The results of this on-going clinical study are anticipated in Q4 2021. In addition to the on-going US clinical trial, we are in preparation of an IND submission to China’s NMPA to initiate a phase 2 "basket" clinical trial in patients with advanced solid tumors in 2H 2021.

Combination therapy with the existing assets for potential new treatment options: Pre-clinical data generated internally and reported by others support the hypothesis that lemzoparlimab may work additive with other immune pathways, such as the CD38 pathway for multiple myeloma, to offer significantly better treatment efficacy for oncology indications. A clinical trial will be initiated in 2H 2021 in China to evaluate safety and efficacy of combination therapy of lemzoparlimab with felzartamab as a possible novel treatment option for relapsed and refractory and newly diagnosed MM, potentially becoming first-line treatment if proven, in addition to felzartamab currently being evaluated as a second-line and third-line treatment for MM.

Potential upcoming milestones:

The on-going clinical trial with lemzoparlimab in combination with pembrolizumab in patients with NSCLC and ovarian cancers in the U.S. is on track to deliver preliminary results by Q4 2021.

A new clinical trial of lemzoparlimab in combination with PD-1 therapy in patients with selected solid tumors will be initiated in 2H 2021 in China.

An abbreviated phase 2 combination study of lemzoparlimab with AZA in untreated AML and MDS patients is planned to commence in Q2 2021 in China. Patient enrollment is expected to complete by Q4 2021.

Topline results from the on-going NHL clinical study, involving both the U.S. and China clinical sites, are expected by Q4 2021.

The combination study of lemzoparlimab with felzartamab in patients with MM is planned to start in 2H 2021 in China.
Uliledlimab (TJD5): A highly differentiated CD73 antibody for immuno-oncology through modulation of tumor microenvironment. Uliledlimab is shown to strongly suppress tumor growth especially when combined with a PD-(L)1 inhibitor in pre-clinical studies. I-Mab has completed a phase 1 clinical trial in the U.S. with positive results for favorable safety, PK/PD, biomarker analysis and clinical activity of uliledlimab. The topline results have been submitted to ASCO (Free ASCO Whitepaper) 2021.

Differentiated mechanism of action by uliledlimab: The Company will present the mechanistic analysis and pre-clinical data at 2021 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting. The key differentiation of uliledlimab when compared to other clinical stage antibodies of the same class is related to its novel epitope, which works through a unique intra-dimer binding mode, resulting in a complete inhibition of the enzymatic activity while avoiding the aberrant pharmacological property known as the "hook effect." With this particular mode of action, uliledlimab has the potential to become a best-in-class CD73 antibody for its clinical advantages.

Phase 1 clinical trial completed in the U.S.: The initial assessment of a phase 1 clinical study investigating uliledlimab monotherapy lead-in followed by combination with atezolizumab (Tecentriq), in patients with solid tumors has been completed. Topline results from the study demonstrate that uliledlimab is safe and well tolerated at the dose range evaluated. The study also demonstrated favorable clinical activity of uliledlimab in patients with advanced solid tumors. I-Mab has submitted an abstract to present the topline results at 2021 ASCO (Free ASCO Whitepaper) annual meeting to be held in June.

Continued clinical development: The Company is looking to expand the on-going clinical study of uliledlimab with a PD-1 antibody toripalimab (TUOYI) in patients with advanced or metastatic cancers in China to further evaluate clinical efficacy of uliledlimab in a phase 2 combination clinical trial with toripalimab in selected solid tumors by a "basket" trial design in 2H 2021.

Potential upcoming milestones:

I-Mab has submitted an abstract to present the phase 1 topline results at the June 2021 ASCO (Free ASCO Whitepaper) annual meeting.

The expansion study in patients with NSCLC and other selected tumors has been initiated in over 15 sites across China. The results are expected in 2022.
Core Clinical Assets – Pre-NDA Products

Felzartamab (TJ202): A potential highly differentiated CD38 antibody for multiple myeloma (MM) and systemic lupus erythematosus (SLE). Felzartamab is a pre-NDA product in I-Mab’s pipeline being positioned to launch in the near-term in China to cover third-line and second-line MM treatment. Its potential role as a first-line MM treatment in combination with lemzoparlimab is being explored.

Multiple myeloma: Two registrational studies of felzartamab are on-going. The third-line registrational trial has completed patient enrollment. The Company is on track to submit an NDA in 2H 2021. The second-line combination therapy with lenalidomide is on track and is continuing to enroll patients. Full patient enrollment (N=291) for that trial is expected in Q3 2021. In addition, a new IND for combination trial of felzartamab with lemzoparlimab for MM will be submitted in Q2 2021 and the study will be initiated in 2H 2021 in China. This combination therapy, a possible first-line treatment if proven, has the potential to be a novel treatment option for relapsed and refractory and newly diagnosed MM.
SLE: The Company is awaiting IND approval by the NMPA and a phase 1b trial in patients with SLE will be initiated 2H 2021 in China.
Potential upcoming milestones:

I-Mab expects to submit an NDA for felzartamab as a third-line treatment for MM to the NMPA in Q4 2021.

Completion of patient enrollment of the second-line registrational study for MM is anticipated in Q3 2021.

In China, a new IND for combination trial of felzartamab with lemzoparlimab as a possible novel treatment option for relapsed and refractory and newly diagnosed MM with the potential to become first-line treatment if proven will be submitted in Q2 2021 and the study will be initiated in 2H 2021.

Initiation of phase 1b SLE trial is on track for 2H 2021.
Eftansomatropin alfa (TJ101): A differentiated long-acting growth hormone for pediatric growth hormone deficiency (PGHD). Eftansomatropin has a product advantage as it is the only rhGH in its proprietary fusion protein format. Its safety and efficacy have been demonstrated in a phase 2 clinical trial in EU.

In February 2021, I-Mab achieved the first patient dosing of a phase 3 registrational clinical trial (NCT04633057) in China to assess the clinical efficacy, safety of eftansomatropin alfa in PGHD patients as a weekly treatment. This registrational phase 3 trial ("TALLER") will enroll 165 patients across multiple centers in China, with the primary objective of demonstrating non-inferiority of 1.2 mg/kg/week of eftansomatropin alfa administered SC, compared to Norditropin, a daily rhGH marketed in China.
Potential upcoming milestones:

The primary clinical data are expected to be available in Q2 2023 to support the planned NDA submission in China.
Efineptakin alfa (TJ107): The world’s first long-acting recombinant human interleukin-7. This asset is positioned clinically as a monotherapy for the treatment of cancer patients with lymphopenia and as a combination immunotherapy to pair with PD-1 or PD-L1 antibody for cancer treatment:

The on-going phase 1b clinical trial in China is investigating the safety, tolerability and PK/PD profile of efineptakin alfa in patients with advanced solid tumors. The results of the study are expected in Q2 2021.
The current clinical development plan is to evaluate the therapeutic role of efineptakin alfa (1) as a monotherapy for cancer patients with lymphopenia and (2) as a combination therapy with PD-1/PD-L1 antibody for cancers. The outcome of the studies will facilitate the development path of efineptakin alfa towards pivotal clinical trials in China.

Cancers with lymphopenia. In December 2020, I-Mab initiated a phase 2 randomized, single-blind, placebo-controlled clinical trial (NCT04600817) to evaluate the safety and efficacy of efineptakin alfa in glioblastoma multiforme (GBM) patients with lymphopenia. The primary outcome of the study is the percentage of patients with an increase in the absolute lymphocyte counts and associated clinical response in relation to the treatment with efineptakin alfa.
Combination therapy with PD-1/PD-L1 agents. Our partner Genexine recently released encouraging new data of a phase 1b/2 study of efineptakin alfa in combination with pembrolizumab (KEYTRUDA) for the treatment of relapsed or refractory triple-negative breast cancer (TNBC) in terms of safety and efficacy signals. I-Mab plans to submit an IND in China in 2H 2021 to initiate a phase 2 clinical trial following a basket trial design, in which efineptakin alfa is combined with a PD-1 antibody for the treatment of selected tumor types, including TNBC.
Other Clinical Assets

Plonmarlimab (TJM2): A granulocyte-macrophage colony stimulating factor (GM-CSF) monoclonal antibody for the treatment of rheumatoid arthritis and CRS-related therapies:

Cytokine release syndrome associated with severe COVID-19: I-Mab is conducting a phase 2 clinical trial with plonmarlimab for the treatment of cytokine release syndrome associated with severe and critically ill COVID-19 patients (NCT04341116) to potentially save lives of patients with severe COVID-19. The clinical trial has progressed to the second part, aiming to evaluate the efficacy, safety and cytokine levels following a single dose of plonmarlimab at 6 mg/kg or placebo (best supportive care) in patients with severe COVID-19. An interim analysis is planned in Q2 2021.
Rheumatoid arthritis: I-Mab has initiated a phase 1b clinical study with plonmarlimab in patients with rheumatoid arthritis (RA). This trial is a multi-center, double-blind, placebo-controlled study involving about 63 patients who will receive a single dose or multiple doses of the treatment for up to eight weeks. The single dose escalation part is aimed to complete by 2H 2021.
Olamkicept (TJ301): A potential highly differentiated IL-6 blocker for ulcerative colitis:

I-Mab has successfully completed a phase 2 study in 91 patients with active ulcerative colitis (UC) in Greater China and South Korea (NCT03235752) and is at the final stages of data analysis.
I-Mab will continue to advance the development and maximize the potential value of this differentiated drug molecule through our global partnership with Ferring.
Enoblituzumab: A potential highly differentiated humanized B7-H3 antibody as an immuno-oncology treatment. I-Mab has the development and commercial rights of enoblituzumab in Greater China from MacroGenics.

I-Mab plans to submit a pre-IND in Q2 2021 to initiate a phase 2 clinical trial of enoblituzumab in combination with a PD-1 antibody in patients with certain tumors in China. The study is designed as a "basket" clinical trial involving NSCLC and two other selected cancer types based on the previous studies conducted by MacroGenics.
I-Mab has plans to evaluate the therapeutic role of enoblituzumab in combination with other targeted cancer therapies as a potential front-line treatment for selected cancers. The pre-clinical work is in progress. Submission of an IND is anticipated by the end of 2021 to start the clinical study.
TJ210: A novel monoclonal antibody targeting myeloid derived suppressor cells as a cancer immunotherapy through a novel mechanism of action. This asset is in clinical development through partnership with MorphoSys.

Pre-clinical development update: TJ210 is a novel human antibody directed against C5aR1 derived from MorphoSys’ HuCAL Platinum technology. The findings of pre-clinical studies in relation to characterization of unique antibody epitope, pharmacological profile and anti-tumor properties of TJ210 were presented at the 2020 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting.

Current clinical development plan: A phase 1 clinical trial is now enrolling patients in the U.S. to evaluate the safety, tolerability and PK/PD profiles of TJ210 in cancer patients. The program is expected to further evolve into a combination clinical trial with a PD-1 antibody in selected cancer types. In addition, with the IND approved by China’s NMPA in February 2021, I-Mab expects to commence a phase 1b clinical trial in 2H 2021. The results of the clinical studies in the U.S. and China, in relation to safety, PK/PD profiles, biomarker analysis and early efficacy signals, as described above will facilitate the further clinical development of TJ210.
Two new bi-specific antibodies have entered the clinical development stage in 2021

TJ-CD4B: A novel bi-specific antibody with the Claudin 18.2 arm as a specific tumor-engager and the 4-1BB arm as a conditional T cell activator upon tumor engagement.

TJ-CD4B is a novel and tumor-dependent bi-specific antibody for the treatment of gastric and other cancers which is being developed under collaboration with ABL Bio. Our pre-clinical studies have demonstrated that TJ-CD4B is capable of binding to tumor cells expressing Claudin 18.2, i.e., gastric cancer and pancreatic cancer cells, and stimulating intra-tumoral T cells by the 4-1BB arm designed to be activated only upon tumor engagement whilst silent elsewhere. Thus, TJ-CD4B effectively maintains a strong tumor binding property and anti-tumor activity attributable to a synergistic effect of both Claudin 18.2 antibody and 4-1BB antibody while it avoids or minimizes liver toxicity and systemic immunotoxicity commonly seen with 4-1BB antibodies as a drug class. I-Mab received the IND approval by the U.S. FDA on March 27, 2021 and aims to commence a phase 1 clinical trial in Q2 2021 in patients with advanced solid tumors including gastric cancer to assess the safety, tolerability, PK/PD and preliminary treatment efficacy. In addition, I-Mab will submit a separate IND with the China NMPA in 2H 2021 by leveraging the clinical data generated from the U.S. study to commence parallel clinical development in China.
TJ-L14B: A differentiated bi-specific antibody with the PD-L1 arm as a tumor-site T cell activator and the 4-1BB arm as a conditional T cell activator upon tumor engagement.

Being developed jointly with ABL Bio, TJ-L14B is a differentiated PD-L1-based bi-specific antibody with the PD-L1 arm as the tumor-dependent T-cell activator and the 4-1BB arm as the conditional T cell activator upon tumor engagement. Pre-clinical tumor animal model studies of TJ-L14B have demonstrated a superior anti-tumor effect attributable to mechanistic synergism of the two antibody arms in activating intra-tumoral T cells. The 4-1BB arm utilizes the same bi-specific antibody format aimed to minimize systemic toxicity as a class effect. With the approved IND from the U.S. FDA, a phase 1 dose escalation clinical study is about to be initiated to assess the safety, tolerability, PK/PD and preliminary efficacy in patients with advanced (unresectable) or metastatic solid tumors.
Pre-Clinical Assets

A number of novel molecules are currently under pre-clinical development, such as: (1) TJX7, a novel monoclonal antibody directed against CXCL13 for the treatment of autoimmune diseases. I-Mab has recently concluded a pre-IND meeting with the U.S. FDA. (2) TJ-C4GM is a fortified CD47 antibody with GM-CSF attached. This antibody-cytokine fusion is designed to enhance the anti-tumor effect of CD47 antibody for solid tumors by activating and converting pro-tumor M2 macrophages to anti-tumor M1 macrophages through the GM-CSF arm. The results of the pre-clinical studies support the novel mechanism of action. (3) TJ-L1I7 is another antibody-cytokine fusion protein with the anti-PDL1 antibody fused with IL-7, which is designed to increase both the number and functionality of T cells drawn to the tumor thereby turning "cold" tumor to more immune-responsive "hot" tumor. (4) TJ-L1C4 belongs to I-Mab’s PD-L1 based bi-specific antibody family and uses CD47 antibody as the other arm. The candidate molecule is being developed at an early pre-clinical stage.
Commercialization Capability

In August 2020, I-Mab appointed Mr. Ivan Yifei Zhu as Chief Commercial Officer, a high-caliber commercial leader in China, to prepare for the market launch of its initial series of products in China.
Our commercialization strategy is designed to build a leading hematologic oncology franchise in China through I-Mab’s unique product portfolio that includes felzartamab (TJ202) for multiple myeloma, lemzoparlimab (TJC4) for various leukemia indications and a late-stage asset/product to be in-licensed to cover lymphoma indications. This unique portfolio of the three key products enables I-Mab to have a near-complete coverage of major disease indications within the hematologic therapeutic area in China and offers an advantageous position to explore a near-cure therapeutic goal for certain hematologic oncology indications through additional drug combinations.
Towards building a leading hematologic oncology franchise in China, I-Mab is laying foundations and progressing efficiently towards becoming an integrated commercial organization, encompassing market access, medical marketing, supply chain and sales teams. The initial effort of the sales organization is to focus on the launch readiness of felzartamab, the Company’s first hematologic oncology product, by targeting top academic centers and hospital networks across China where the target patient population accounting for majority of national cases is concentrated.
Manufacturing Facility

I-Mab has made significant progress in building a comprehensive biologics manufacturing facility in Hangzhou, China (the "Hangzhou Facility").
The Hangzhou Facility aims to have a pilot plant capacity of 2 production lines (1 line configured with 2 x 2,000L and another line with 1 x 2,000L) by 2022 and commercially progressive capacity up to 8 x 4,000L to become operational by the end of 2023.
The Hangzhou Facility, when operational, will exclusively serve I-Mab’s increasing CMC and manufacturing needs for all on-going and future clinical trials in the U.S. and China and the sustained production of its planned commercial products. The Hangzhou Facility will enable the Company to control the quality and manufacturing schedules tailored to its development and commercialization needs. Importantly, it will significantly reduce our production cost burden and cost of goods as a whole.
Corporate Achievements

In March 2021, I-Mab reported substantial net revenues of RMB 1,542.7 million (US $236.4 million) and net income on a GAAP basis of RMB 470.9 million (US $72.2 million) for the full year of 2020, achieving corporate profitability for the first time in the Company’s history.
In March 2021, I-Mab secured collaborations with Complix, an EU-based biotech company, and Affinity, a Shanghai-based biotech company, gaining access to cutting edge technology platforms to develop its next generation of novel and highly differentiated drug candidates.
In December 2020, I-Mab’s American Depositary Shares (ADS) were selected for inclusion in the NASDAQ Biotechnology Index (Nasdaq: .NBI), based on a set of eligibility criteria including minimum market capitalization and average daily trading volume.
In December 2020, I-Mab appointed leading Immunology and Hematology experts Dr. Chen Dong and Dr. Jun Ma to its Scientific Advisory Board.
In November 2020, I-Mab received BioCentury-Bay Helix’s "Deal of the Year" award for the global strategic collaboration with AbbVie to develop and commercialize lemzoparlimab. I-Mab was also named "10 Biotechs to Know in China" by FiercePharma and listed as "50 Smartest Companies in China" by MIT Technology Review.
In September 2020, I-Mab raised approximately US$418 million through a private placement by a consortium of institutional investors led by Hillhouse Capital.
In September 2020, I-Mab and AbbVie entered into a strategic global collaboration to develop and commercialize lemzoparlimab (TJC4). The total upfront plus milestone payments as well as the potential value of the right of first negotiation in relation to the two additional CD47-based bi-specific antibodies amounted to US $2.94 billion, making this deal the largest cross-border out-licensing transaction from China by total value.
In May 2020, I-Mab opened its Hong Kong office as a regional hub for capital markets and investor relations activities, further benefiting from the Greater Bay Area economic development initiative in the region.
Full Year 2020 Financial Results

Cash Position

As of December 31, 2020, the Company had cash, cash equivalents, restricted cash and short-term investments of RMB 4.8 billion (US $734.1 million), compared with RMB 1.2 billion as of December 31, 2019. The current cash on hand is sufficient to fund operations through 2023, including data readouts on core clinical assets such as lemzoparlimab and uliledlimab and commercialization in China of pre-NDA assets felzartamab and efineptakin alfa.

Net Revenues

Total net revenues for the full year of 2020 were RMB 1,542.7 million (US $236.4 million), compared with RMB 30.0 million for the full year of 2019. The revenues generated for the full year of 2020 solely consisted of the revenues recognized in connection with the strategic collaboration with AbbVie.

Research & Development Expenses

Research and development expenses for the full year of 2020 were RMB 984.7 million (US $150.9 million), compared with RMB 840.4 million for the full year of 2019. The increase was primarily due to the increase in employee benefit expenses, which consist of share-based compensation and payroll expenses, to support expansion of research and development programs.

Administrative Expenses

Administrative expenses for the full year of 2020 were RMB 402.4 million (US $61.7 million), compared with RMB 654.6 million for the full year of 2019. The decrease was primarily due to reduced share-based compensation expenses of RMB 305.7 million (US $46.9 million).

Other Income (Expenses), net

Net other income for the full year of 2020 was RMB 412.9 million (US $63.3 million), compared with net other expenses of RMB 20.2 million for the full year of 2019. The change was primarily attributable to the RMB 407.6 million gain recognized as a result of the transfer of equity of I-Mab Hangzhou from I-Mab Hong Kong to a group of domestic investors in China. The equity transfer realized the fair value appreciation in the pipeline assets as well as the employment of a team of designated management and workforce.

Net Income

Net income for the full year of 2020 was RMB 470.9 million (US $72.2 million), compared with a loss of RMB 1,452.0 million for the full year of 2019. Net income per share attributable to ordinary shareholders for the full year of 2020 was RMB 3.51 (US $0.54), compared with net loss per share attributable to ordinary shareholders of RMB 201.19 for the full year of 2019. Net income per ADS attributable to ordinary shareholders for the full year of 2020 was RMB 8.07 (US $1.24), compared with net loss per ADS attributable to ordinary shareholders of RMB 462.74 for the full year of 2019.

Non-GAAP Net Income

Non-GAAP adjusted net income, which excludes share-based compensation expenses, for the full year of 2020 was RMB 997.1 million (US $152.8 million), compared with non-GAAP adjusted net loss of RMB 936.7 million for the full year of 2019. Non-GAAP adjusted net income per share attributable to ordinary shareholders for 2020 was RMB 7.43 (US $1.14), compared with non-GAAP adjusted net loss per share attributable to ordinary shareholders of RMB 131.39 for the full year of 2019. Non-GAAP adjusted net income per ADS attributable to ordinary shareholders for the full year of 2020 was RMB 17.09 (US $2.62), compared with non-GAAP adjusted net loss per ADS attributable to ordinary shareholders of RMB 302.20 for the full year of 2019.

Conference Call and Webcast Information

The Company will host a live conference call and webcast on March 29, 2020 at 8:00 a.m. ET. Participants must register in advance of the conference call. Details are as follows:

Registration Link: View Source

Conference ID: 4848159
Upon registering, each participant will receive a dial-in number, Direct Event passcode, and a unique access PIN, which can be used to join the conference call.

A webcast replay will be archived on the Company’s website for one year after the conclusion of the call at View Source

A telephone replay will be available approximately two hours after the conclusion of the call. To access the replay, please call +1-855-452-5696 (U.S.), +61-2-8199-0299 (International), 400-632-2162 (Mainland China), or 800-963-117 (Hong Kong). The conference ID number for the replay is 4848159.