8 unchanged sentences
We believe this integrated CDx and Rx strategy will maximize the impact our CELsignia platform has on the treatment landscape for cancer patients.
−Removed: Our proprietary CELsignia diagnostic platform is the only commercially ready technology we are aware of that uses a patient’s living tumor cells to identify the specific abnormal cellular process driving a patient’s cancer and the targeted therapy that best treats it.
−Removed: This enables us to identify patients whose tumors may respond to a targeted therapy, even though they lack a previously associated molecular mutation.
−Removed: By identifying cancer patients whose tumors lack an associated genetic mutation but have abnormal cellular activity a matching targeted therapeutic is designed to inhibit, CELsignia CDx can expand the markets for a number of already approved targeted therapies.
−Removed: Our current CDx identifies breast and ovarian cancer patients whose tumors have cancer drivers potentially responsive to treatment with human epidermal growth factor receptor 2-negative (HER2), mesenchymal-epithelial transition factor (c-MET), or phosphatidylinositol 3-kinases (PI3K) targeted therapeutics.
−Removed: Our CELsignia platform provides an important advantage over traditional molecular diagnostics.
−Removed: Current molecular diagnostics analyze fragmented cells to obtain a snapshot of the genetic mutations present in a patient’s tumor.
−Removed: Using cell fragments prevents molecular diagnostics from analyzing the dynamic cellular activities, known as cell signaling, that regulate cell proliferation or survival.
−Removed: Cancer can develop when critical cell signaling, regulating physiologic activity such as cell proliferation, becomes abnormal or dysregulated.
−Removed: Since genetic mutations are often only weakly correlated to the dysregulated cell signaling activity driving a patient’s cancer, a molecular diagnostic is prone to providing an incomplete diagnosis.
−Removed: CELsignia tests overcome this limitation by measuring dynamic cell signaling activity in a cancer patient’s living tumor cells.
−Removed: When a CELsignia test detects abnormal signaling activity, a more accurate diagnosis of the patient’s cancer driver is obtained.
−Removed: We are supporting the advancement of new potential indications for six different targeted therapies, controlled by other pharmaceutical companies, that would rely on a CELsignia CDx to select patients.
−Removed: Five Phase 2 trials are underway to evaluate the efficacy and safety of these therapies in CELsignia selected patients.
−Removed: These patients are not currently eligible to receive these drugs and are not identifiable with a molecular test.
The first drug candidate we are developing internally is gedatolisib, a potent, well-tolerated, small molecule dual inhibitor, administered intravenously, that selectively targets all Class 1 isoforms of PI3K and mammalian target of rapamycin (mTOR).
14 unchanged sentences
CELsignia Development and CDx Programs
+Added: Our proprietary CELsignia diagnostic platform is the only commercially ready technology we are aware of that uses a patient’s living tumor cells to identify the specific abnormal cellular process driving a patient’s cancer and the targeted therapy that best treats it.
+Added: This enables us to identify patients whose tumors may respond to a targeted therapy, even though they lack a previously associated molecular mutation.
+Added: By identifying cancer patients whose tumors lack an associated genetic mutation but have abnormal cellular activity a matching targeted therapeutic is designed to inhibit, CELsignia CDx can expand the markets for a number of already approved targeted therapies.
+Added: Our current CDx identifies breast and ovarian cancer patients whose tumors have cancer drivers potentially responsive to treatment with human epidermal growth factor receptor 2-negative (HER2), mesenchymal-epithelial transition factor (c-MET), or phosphatidylinositol 3-kinases (PI3K) targeted therapeutics.
+Added: Food and Drug Administration (“FDA”) approval or clearance is not currently required for CELsignia tests offered as a stand-alone laboratory developed test, if we are partnered with a drug company to launch a CELsignia test as a companion diagnostic for a new drug indication, we would be required to obtain premarket approval, or PMA, in conjunction with the pharmaceutical company seeking a new drug approval for the matching therapy.
+Added: Our CELsignia platform provides an important advantage over traditional molecular diagnostics.
+Added: Current molecular diagnostics analyze fragmented cells to obtain a snapshot of the genetic mutations present in a patient’s tumor.
+Added: Using cell fragments prevents molecular diagnostics from analyzing the dynamic cellular activities, known as cell signaling, that regulate cell proliferation or survival.
+Added: Cancer can develop when critical cell signaling, regulating physiologic activity such as cell proliferation, becomes abnormal or dysregulated.
+Added: Since genetic mutations are often only weakly correlated to the dysregulated cell signaling activity driving a patient’s cancer, a molecular diagnostic is prone to providing an incomplete diagnosis.
+Added: CELsignia tests overcome this limitation by measuring dynamic cell signaling activity in a cancer patient’s living tumor cells.
+Added: When a CELsignia test detects abnormal signaling activity, a more accurate diagnosis of the patient’s cancer driver is obtained.
+Added: We are supporting the advancement of new potential indications for six different targeted therapies, controlled by other pharmaceutical companies, that would rely on a CELsignia CDx to select patients.
+Added: Five Phase 2 trials are underway to evaluate the efficacy and safety of these therapies in CELsignia selected patients.
+Added: These patients are not currently eligible to receive these drugs and are not identifiable with a molecular test.
Our first analytically validated and commercially ready test using our CELsignia platform, the CELsignia HER2 Pathway Activity Test for breast cancer, diagnoses two new sub-types of HER2-negative breast cancer that traditional molecular diagnostics cannot detect.
5 unchanged sentences
These studies suggest that this sub-group of HER2-negative breast cancer patients may best respond to treatment with a combination of HER family and c-Met inhibitors.
+Added: We have two interventional clinical trials underway to evaluate the efficacy of HER2 and c-Met targeted therapies, in previously treated metastatic HER2-negative breast cancer patients selected with our CELsignia Multi-Pathway Activity Test, or CELsignia MP Test.
Our third CELsignia test for breast cancer evaluates PI3K signaling in HER2-negative breast cancer tumor cells.
8 unchanged sentences
As a companion diagnostic, our CELsignia test for ovarian cancer will be intended to help pharmaceutical companies obtain new drug indications and expand treatment options for this challenging tumor type.
−Removed: We initiated discussions with pharmaceutical companies about collaborating on clinical trials in late 2020.
−Removed: We also made significant progress in 2020 developing a new CELsignia test intended to diagnose cancers driven by dysregulated RAS signaling.
−Removed: Dysregulation of RAS signaling, which includes the RAF/MEK/ERK and PI3K/AKT/mTOR pathways, is estimated to drive 30%-40% of all cancers.
−Removed: Pharmaceutical companies have developed numerous drugs that target RAS-involved pathways.
−Removed: However, the number of interactions amongst RAS-regulated pathways has made it extremely difficult to use molecular tests to identify patients with dysregulated RAS signaling tumors.
−Removed: The challenge of diagnosing a cancer driven by a dysregulated RAS signaling network is magnified because two or more different pathways are typically involved.
−Removed: Recent research has also found that RAS mutations play a much less important role in dysregulated RAS signaling than previously thought.
−Removed: Our CELsignia platform is uniquely suited to untangle the complexity of dysregulated RAS signaling tumors and identify the targeted therapy combination capable of treating it.
−Removed: Once development of the new RAS test is completed, we intend to add it to our current CELsignia MP Test for breast and ovarian cancer.
−Removed: This next generation CELsignia test would provide an analysis of EGFR/HER1, HER2, HER3, c-MET, PI3K, and RAS-involved signaling activity for each patient tumor specimen received.
+Added: We are currently in discussions with pharmaceutical companies about collaborating on future clinical trials.
In addition to our CELsignia tests for HER2-negative breast cancer and ovarian cancer, we expect to develop CELsignia tests to diagnose eight new potential cancer sub-types we have discovered in lung, ovarian, kidney, and bladder cancers.
2 unchanged sentences
Our overall commercialization strategy is to develop diagnostics that expand the patient population eligible for targeted therapies.
−Removed: We are collaborating with Genentech, Pfizer, Novartis, and Puma to conduct five Phase 2 clinical trials to evaluate the efficacy of our collaboration partners’ targeted therapies in patients selected with one of our CELsignia tests.
+Added: In furtherance of this strategy, we will seek collaborations with pharmaceutical companies to field clinical trials to advance the clinical development of their targeted therapies with the eventual goal of obtaining FDA approval of a new drug indication.
+Added: Collaborations are expected to involve initially Phase I or Phase II interventional clinical trials to evaluate the efficacy of our collaboration partners’ targeted therapies on patients selected with one of our CELsignia tests.
+Added: These trials would not be intended to separately evaluate the CELsignia tests, whether as standalone tests or companion diagnostics.
+Added: While FDA approval or clearance is not currently required for CELsignia tests offered as a stand-alone laboratory developed test, if we are partnered with a drug company to launch a CELsignia test as a companion diagnostic for a new drug indication, we would be required to obtain premarket approval, or PMA, in conjunction with the pharmaceutical company seeking a new drug approval for the matching therapy.
+Added: We are currently collaborating on five Phase II clinical trials to evaluate the efficacy of our collaboration partners’ targeted therapies in patients selected with one of our CELsignia tests.
The goal of these trials is to support the development of five potential new drug indications to treat patient groups found responsive by our CELsignia test to their approved targeted therapies.
−Removed: Our CELsignia MP Test analyzes HER2, c-MET, and PI3K signaling activity using a patient’s live tumor cells.
−Removed: These tests have the potential to diagnose oncogenic signaling activity undetectable by molecular tests in up to one in three HER2-negative breast cancer patients and one in five ovarian cancer patients.
−Removed: We intend to use this test to identify HER2-negative breast cancer patients whose tumors have either abnormal HER2 signaling, abnormal c-Met and HER2 signaling, or abnormal PI3K signaling.
−Removed: Our overall commercialization strategy for our CELsignia CDx is to collaborate with pharmaceutical companies to advance the clinical development of their targeted therapies with the eventual goal of obtaining FDA approval of a new drug indication.
−Removed: Our current programs include:
−Removed: Herceptin ® and Perjeta ® for HER2-negative early-stage breast cancer patients.
−Removed: Each drug targets the HER2 receptor and is owned by Genentech, Inc.
−Removed: These drugs are only currently approved to treat cancer patients who are HER2+.
−Removed: Vizimpro ® and Xalkori ® for HER2-negative late-stage breast cancer patients.
−Removed: Vizimpro, a pan-HER inhibitor, and Xalkori, a c-Met inhibitor, are owned by Pfizer, Inc.
−Removed: These drugs are currently only approved to treat patients with non-small cell lung cancer who have specific molecular mutations.
−Removed: Tabrecta ® and Nerlynx ® for HER2-negative late-stage breast cancer patients.
−Removed: Tabrecta, a c-Met inhibitor, is owned by Novartis AG and Nerlynx is owned by Puma Biotechnology, Inc.
−Removed: Tabrecta is currently only approved to treat patients with non-small cell lung cancer who have specific molecular mutations.
−Removed: Nerlynx is currently only approved to treat HER2+ breast cancer patients.
−Removed: Nerlynx and Faslodex for ER+/HER2-negative late-stage breast cancer patients.
−Removed: Faslodex, a selective estrogen receptor degrader, is owned by AstraZeneca.
−Removed: Nerlynx for ER-/HER2- early-stage breast cancer patients.
−Removed: Interventional Clinical Trials in Process using a CELsignia Test to Select Patients for Treatment
−Removed: FACT-1 Clinical Trial to Evaluate Efficacy of Genentech’s HER2 Targeted Therapies
−Removed: We are collaborating with NSABP and Genentech to evaluate the efficacy and safety of Genentech’s drugs, Herceptin (trastuzumab) and Perjeta (pertuzumab), and chemotherapy in breast cancer patients selected with our CELsignia test.
−Removed: NSABP serves as the sponsor and principal investigator of the trial and is responsible for, among other things, setting up clinical sites, enrolling patients, and managing clinical data.
−Removed: NSABP contracted separately with Genentech to provide Herceptin and Perjeta for the study at no cost.
−Removed: We are performing the CELsignia HER2 Pathway Activity Test to select patients for the trial and are providing the funding for the trial’s patient-related costs.
−Removed: Completing this trial will require, among other things, successful enrollment of patients, meeting trial endpoint goals, and completing the trial in a timely manner.
−Removed: As of February 2021, there were 27 activated sites participating in the FACT-1 trial.
−Removed: The enrollment rate of patients has fallen short of the expectations NSABP originally provided.
−Removed: Based on NSABP’s updated estimates of patient enrollment rates to reflect the impact of COVID-19, we expect to obtain interim results late 2021 or early 2022 and final results approximately nine months later.
+Added: These clinical trials include:
+Added: FACT-1 Clinical Trial to Evaluate Efficacy of Genentech’s HER2 Targeted Therapies – We are collaborating with NSABP Foundation, Inc.
+Added: (“NSABP”) and Genentech, Inc.
+Added: (“Genentech”) to evaluate the efficacy and safety of Genentech’s drugs, Herceptin (trastuzumab) and Perjeta (pertuzumab), and chemotherapy in breast cancer patients selected with our CELsignia test.
+Added: Based on NSABP’s updated estimates of patient enrollment rates to reflect the impact of COVID-19, interim results are expected in late 2021 or early 2022 and final results approximately nine months later.
The goal is to demonstrate that patients who have an abnormal HER2 signaling pathway, as identified by our CELsignia test, respond to treatment with a matching targeted therapy.
−Removed: A synopsis of the trial protocol is provided below.
−Removed: FACT-1 Clinical Trial Synopsis
−Removed: Primary Objective
−Removed: To evaluate the efficacy of neoadjuvant HER2 drug treatment in early-stage HER2-negative breast cancer patients with abnormal HER2 signaling
−Removed: Sites/Sponsor
−Removed: Investigational Arm
−Removed: Multi-center in collaboration with NSABP and Genentech
−Removed: 54 HER2-negative early-stage breast cancer (26 ER+/28ER-)
−Removed: Pathological complete response (ypT0/Tis ypN0)
−Removed: AC-T + Trastuzumab + Pertuzumab
−Removed: FACT-2 Clinical Trial to Evaluate Efficacy of Puma’s HER2 Targeted Therapy
−Removed: We are collaborating with Puma and West Cancer Center to conduct a Phase II single-arm interventional trial to evaluate the efficacy and safety of Puma’s drug, Nerlynx (neratinib), and chemotherapy in breast cancer patients selected with our CELsignia test.
−Removed: West Cancer Center serves as the sponsor and principal investigator of the trial and is responsible for enrolling patients and managing clinical data.
−Removed: Puma supplies Nerlynx, its pan-HER inhibitor currently approved by the FDA for extended adjuvant treatment of early-stage HER2-positive breast cancer.
−Removed: We provide the CELsignia HER2 Pathway Activity Test to select triple-negative breast cancer patients who have hyperactive HER2-driven signaling pathways for the trial and will initially fund the patient-related trial costs.
−Removed: Based on West Cancer Center estimates to reflect the impact of COVID-19, we expect interim results from this trial in late 2021 or early 2022 and final results approximately nine months later.
+Added: FACT-2 Clinical Trial to Evaluate Efficacy of Puma’s HER2 Targeted Therapy – We are collaborating with Puma Biotechnology, Inc.
+Added: (“Puma”) and West Cancer Center to conduct a Phase II single-arm interventional trial to evaluate the efficacy and safety of Puma’s drug, Nerlynx (neratinib), and chemotherapy in breast cancer patients selected with our CELsignia test.
+Added: Based on West Cancer Center’s updated estimates of patient enrollment rates to reflect the impact of COVID-19, interim results are expected in late 2021 or early 2022 and final results approximately nine months later.
The goal of the trial is to demonstrate that triple-negative breast cancer patients who have a hyperactive HER2 signaling tumor, as identified by the CELsignia test, respond to treatment with Nerlynx, a matching HER2 therapy.
−Removed: We believe there is significant clinical interest in finding new diagnostic tests and targeted therapies for triple-negative breast cancer patients because fewer drug treatment options are available to them relative to other breast cancer sub-types.
−Removed: A synopsis of the trial protocol is provided below.
−Removed: FACT-2 Clinical Trial Synopsis
−Removed: Primary Objective
−Removed: To evaluate the efficacy of neoadjuvant HER2 drug treatment in early-stage triple-negative breast cancer patients with abnormal HER2 signaling
−Removed: Sites/Sponsor
−Removed: Investigational Arm
−Removed: Multi-center in collaboration with West Cancer Center and Puma
−Removed: 27 early-stage triple-negative breast cancer with abnormal HER2 signaling
−Removed: Pathological complete response (ypT0/Tis ypN0)
−Removed: Neratinib then Paclitaxel + Carboplatin + Neratinib
−Removed: FACT-3 Clinical Trial to Evaluate Efficacy of Pfizer’s pan-HER and c-Met Targeted Therapies
−Removed: In January 2021, we announced a clinical trial collaboration with Sarah Cannon Research Institute, a global leader in cancer research, and Pfizer Inc., a global biopharmaceutical company, to conduct a Phase II clinical trial.
+Added: FACT-3 Clinical Trial to Evaluate Efficacy of Pfizer’s pan-HER and c-Met Targeted Therapies – In January 2021, we announced a clinical trial collaboration with Sarah Cannon Research Institute and Pfizer to conduct a Phase II clinical trial.
This open-label Phase II trial will evaluate the efficacy and safety of two Pfizer targeted therapies, Vizimpro (dacomitinib), a pan-HER inhibitor, and Xalkori (crizotinib), a c-Met inhibitor, in previously treated metastatic HER2-negative breast cancer patients selected with our CELsignia Multi-Pathway Activity Test.
−Removed: Under the agreement, Sarah Cannon will serve as the sponsor and principal investigator of the trial and will be responsible for enrolling patients and managing clinical data.
−Removed: Pfizer will supply Vizimpro and Xalkori, targeted therapies currently approved by the FDA to treat metastatic non-small cell lung cancer.
−Removed: We will provide our CELsignia Multi-Pathway Activity Test to select HER2- metastatic breast cancer patients who have hyperactive HER2 and c-Met signaling pathways for the trial and will fund the patient-related trial costs.
−Removed: Based on the Sarah Cannon Research Institute’s estimates of patient enrollment rates, we expect to obtain interim results 12 to 15 months after the protocol is activated and final results 12-15 months later.
−Removed: We expect enrollment to begin in the second or third quarter of 2021.
+Added: Based on the Sarah Cannon Research Institute’s estimates of patient enrollment rates, interim results are expected 12-15 months after the protocol is activated and final results 12-15 months later.
+Added: We expect enrollment to begin in the third quarter of 2021.
The goal of the trial is to demonstrate that previously treated HER2-negative metastatic breast cancer patients who have hyperactive HER2 and c-Met signaling tumors, as identified by the CELsignia test, respond to treatment with Vizimpro in combination with Xalkori.
−Removed: We believe there is significant clinical interest in finding new diagnostic tests and targeted therapies for metastatic HER2-negative breast cancer patients whose disease progressed on prior therapies.
−Removed: The anti-tumor effect of blockading EGFR/HER1, HER2, HER3 and c-Met pathways when the HER2 and c-Met pathways are hyperactive has been demonstrated in animal models.
−Removed: A synopsis of the trial protocol is provided below.
−Removed: FACT-3 Clinical Trial Synopsis
−Removed: Primary Objective
−Removed: To assess the efficacy of combined Vizimpro plus Xalkori in previously treated HER2-negative metastatic breast cancer subjects with hyperactive HER2 and c-Met signaling tumors
−Removed: Sites/Sponsor
−Removed: Investigational Arm
−Removed: Multi-center in collaboration with Sarah Cannon Research Institute and Pfizer
−Removed: 23 late-stage HER2-negative breast cancer with abnormal HER2/c-Met signaling
−Removed: Objective response using RECIST 1.1 criteria
−Removed: Vizimpro and Xalkori
−Removed: FACT-4 Clinical Trial to Evaluate Efficacy of Puma’s HER2 Targeted Therapy
−Removed: In December 2020, we announced a clinical trial collaboration with Massachusetts General Hospital and Puma Biotechnology, a biopharmaceutical company, to conduct a Phase II clinical trial.
+Added: FACT-4 Clinical Trial to Evaluate Efficacy of Puma’s HER2 Targeted Therapy – In December 2020, we announced a clinical trial collaboration with Massachusetts General Hospital and Puma, a biopharmaceutical company, to conduct a Phase II clinical trial.
This open-label Phase II trial will evaluate the efficacy and safety of Puma’s drug, Nerlynx (neratinib), and Faslodex (fulvestrant), an AstraZeneca drug, in previously treated metastatic HR-positive (HR+), HER2-negative breast cancer patients selected with our CELsignia HER2 Pathway Activity Test.
−Removed: Under the agreement, Massachusetts General Hospital will serve as the sponsor and the principal investigator of this study, while the UCLA Jonsson Comprehensive Cancer Center and the Vanderbilt-Ingram Cancer Center will serve as co-sponsors.
−Removed: Each of these institutions is amongst the United States’ 51 NCI-Designated Comprehensive Cancer Centers tasked with developing new approaches to diagnosing and treating cancer.
−Removed: Puma will supply Nerlynx, its HER2 inhibitor currently approved by the FDA for early and late-stage HER2-positive breast cancer.
−Removed: We will provide our CELsignia HER2 Pathway Activity Test to select HR+, HER2-negative metastatic breast cancer patients who have hyperactive HER2-driven signaling pathways for the trial and will fund the patient-related trial costs.
−Removed: Based on Massachusetts General Hospital’s estimates of patient enrollment rates, we expect to obtain interim results 12 to 15 months after the protocol is activated and final results 12 to 15 months later.
−Removed: We expect enrollment to begin in the second quarter of 2021.
+Added: Based on Massachusetts General Hospital’s estimates of patient enrollment rates, we expect to obtain interim results 12-15 months after the protocol is activated and final results 12 to 15 months later.
+Added: We expect enrollment to begin in the third quarter of 2021.
The goal of the trial is to demonstrate that previously treated HR+, HER2-negative metastatic breast cancer patients who have hyperactive HER2 signaling tumors, as identified by the CELsignia test, respond to treatment with Nerlynx in combination with Faslodex, a hormonal therapy that targets the estrogen receptor.
−Removed: We believe there is significant clinical interest in finding new diagnostic tests and targeted therapies for metastatic HR+, HER2-negative breast cancer patients whose disease progressed on prior therapies.
−Removed: Of particular interest are new therapeutic combinations that can overcome resistance to anti-estrogen therapies like Faslodex.
−Removed: The blockade of estrogen receptor and HER2 pathways when the HER2 pathway is hyperactive using a combination of Neratinib and Faslodex has been demonstrated in animal models.
−Removed: A synopsis of the trial protocol is provided below.
−Removed: FACT-4 Clinical Trial Synopsis
−Removed: Primary Objective
−Removed: To assess the efficacy of combining Nerlynx plus Faslodex in previously treated metastatic HR-positive, HER2-negative patients with hyperactive HER2 signaling tumors
−Removed: Sites/Sponsor
−Removed: Investigational Arm
−Removed: Multi-center in collaboration with Mass General and Puma
−Removed: 23 late-stage HR+/HER2-negative breast cancer with abnormal HER2 signaling
−Removed: Objective response using RECIST 1.1 criteria
−Removed: Nerlynx and Faslodex
−Removed: FACT-6 Clinical Trial to Evaluate Efficacy of Novartis’s c-Met Inhibitor and Puma’s pan-HER inhibitor
−Removed: In March 2021, we announced a clinical trial collaboration with MD Anderson, a global leader in cancer research, Novartis AG, a global biopharmaceutical company, and Puma Biotechnology, to conduct a Phase I/II clinical trial.
+Added: FACT-6 Clinical Trial to Evaluate Efficacy of Novartis’s c-Met Inhibitor and Puma’s pan-HER Inhibitor – In March 2021, we announced a clinical trial collaboration with MD Anderson, Novartis AG, and Puma, to conduct a Phase I/II clinical trial.
This open-label Phase I/II trial will evaluate the efficacy and safety of Novartis’ c-Met inhibitor, Tabrecta (capmatinib), and Puma’s pan-HER inhibitor, Nerlynx (neratinib), in previously treated metastatic HER2-negative breast cancer patients selected with our CELsignia Multi-Pathway Activity Test.
−Removed: Under the agreement, MD Anderson will serve as the sponsor of the trial and will be responsible for enrolling patients and managing clinical data.
−Removed: Novartis will supply Tabrecta, a targeted therapy currently approved by the FDA to treat metastatic non-small cell lung cancer.
−Removed: Puma will supply Nerlynx, a targeted therapy currently approved by the FDA to treat HER2+ metastatic breast cancer.
−Removed: We will provide our CELsignia Multi-Pathway Activity Test to select HER2- metastatic breast cancer patients who have hyperactive HER2 and c-Met signaling pathways for the trial and will fund the patient-related trial costs.
−Removed: Based on MD Anderson’s estimates of patient enrollment rates, we expect to obtain interim results 12 to 15 months after the protocol is activated and final results 12-15 months later.
−Removed: We expect enrollment to begin in the second or third quarter of 2021.
+Added: Based on MD Anderson’s estimates of patient enrollment rates, we expect to obtain interim results 12-15 months after the protocol is activated and final results 12-15 months later.
+Added: We expect enrollment to begin in the third quarter of 2021.
The goal of the trial is to demonstrate that previously treated HER2-negative metastatic breast cancer patients who have hyperactive HER2 and c-Met signaling tumors, as identified by the CELsignia test, respond to treatment with Tabrecta in combination with Nerlynx.
−Removed: We believe there is significant clinical interest in finding new diagnostic tests and targeted therapies for metastatic HER2-negative breast cancer patients whose disease progressed on prior therapies.
−Removed: The anti-tumor effect of blockading EGFR/HER1, HER2, HER3 and c-Met pathways when the HER2 and c-Met pathways are hyperactive has been demonstrated in animal models.
−Removed: A synopsis of the trial protocol is provided below.
−Removed: FACT-6 Clinical Trial Synopsis
−Removed: Primary Objective
−Removed: To assess the efficacy of combined Tabrecta plus Nerlynx in previously treated HER2-negative metastatic breast cancer subjects with hyperactive HER2 and c-Met signaling tumors
−Removed: Sites/Sponsor
−Removed: Investigational Arm
−Removed: Multi-center in collaboration with MD Anderson, Novartis, and Puma
−Removed: Up to 48 late-stage HER2-negative breast cancer with abnormal HER2/c-Met signaling
−Removed: Objective response using RECIST 1.1 criteria
−Removed: Tabrecta and Nerlynx
−Removed: In conjunction with the development of our CELsignia tests, we will seek collaborations with pharmaceutical companies to field clinical trials to advance the clinical development of their targeted therapies with the eventual goal of obtaining U.S.
−Removed: Food and Drug Administration (“FDA”) approval of a new drug indication.
−Removed: Collaborations are expected to involve initially Phase I or Phase II interventional clinical trials to evaluate the efficacy of our collaboration partners’ targeted therapies patients selected with one of our CELsignia tests.
−Removed: We are currently evaluating, or expect to evaluate, a variety of targeted therapies in combination with other targeted therapies, hormonal therapies, of chemotherapies, including:
−Removed: i) pan-HER and c-Met inhibitors;
−Removed: ii) pan-HER inhibitors and endocrine therapy;
−Removed: iii) pan-HER inhibitors and chemotherapies;
−Removed: and iv) PI3K inhibitors and endocrine therapy.
−Removed: The FDA has approved three c-Met inhibitors, six HER-family inhibitors, and four PI3K inhibitors for cancer treatment.
−Removed: Additional c-Met, HER-family, and PI3K inhibitors are being evaluated in on-going clinical trials.
−Removed: Gedatolisib – An Internal Drug Candidate
+Added: Therapeutic (Rx) Product Development
Gedatolisib (PF-05212384) is a potent, reversible dual inhibitor that selectively targets PI3K and mTOR.
4 unchanged sentences
Based on the favorable preliminary results reported to date from the Phase 1b trial, we intend to initiate, subject to feedback from the FDA, a Phase 2/3 clinical trial evaluating gedatolisib in combination with palbociclib and an endocrine therapy in patients with ER+/HER2- advanced or metastatic breast cancer in the first half of 2022.
−Removed: Background on Breast Cancer and Current Treatments
Breast cancer is the most prevalent cancer in women, accounting for 30% of all female cancers and 13% of cancer-related deaths in the United States.
4 unchanged sentences
Despite progress in treatment strategies, metastatic ER+/HER2- breast cancer (mBC) remains an incurable disease, with a median overall survival (OS) of three years and a five-year survival rate of 25%.
−Removed: Four different classes of targeted therapies are currently used to treat ER+/HER2- tumors.
−Removed: These drugs generated revenues of nearly $10 billion globally in 2019.
−Removed: Endocrine-based therapies .
−Removed: Selective ER modulators (tamoxifen), selective ER degrader (fulvestrant), and aromatase inhibitors (AIs) are established standards of care in women with HR+/HER2- mBC.
−Removed: The choice between these regimens when treating mBC depends on the type and duration of prior endocrine therapy treatment as well as the time elapsed from the end of prior endocrine therapy.
−Removed: Besides the well-known efficacy of these treatments as first-line therapies in women without visceral crisis, most patients develop endocrine resistance leading to therapeutic failure.
−Removed: Primary endocrine resistance is defined as relapse during the first two years of prior endocrine therapy or progressive disease within the first six months of first-line endocrine therapy for mBC.
−Removed: Secondary resistance is present (1) when a relapse occurs after the first two years of adjuvant endocrine therapy;
−Removed: (2) when a relapse occurs within 12 months of completing adjuvant endocrine therapy;
−Removed: or (3) when a progressive disease occurs after more than six months from the beginning of endocrine therapy for mBC.
−Removed: Several mechanisms are responsible for endocrine resistance, including the dysregulation of multiple components of the ER pathway (aberration in ER expression, over-expression of ER co-activators, and down-regulation of co-repressors), altered regulation of signaling molecules involved in cell cycle or cell survival, and the activation of escape pathways that can provide cell replication.
−Removed: CDK4/6 inhibitors .
−Removed: One common mechanism of resistance to endocrine therapies is the activation of the cyclin-dependent kinases 4 and 6 (CDK4/6) pathway.
−Removed: These kinases drive cell cycle progression and division.
−Removed: Inhibiting activation of the CDK4/6 prevents estrogen from activating the cyclin D1-CDK4/6-Rb complex, thus blockading an important mechanism of resistance to endocrine therapies.
−Removed: The resulting cell cycle arrest induces a significant delay in tumor progression.
−Removed: CDK 4/6 inhibitors were first introduced in 2015.
−Removed: Endocrine therapies administered in combination with oral CDK4/6 inhibitors lead to improved clinical efficacy when compared with endocrine therapies as monotherapy.
−Removed: In two randomized, double-blind clinical trials, treatment of HR+/HER2- advanced breast cancer patients with a combination of palbociclib and either letrozole or fulvestrant demonstrated a significant increase in the median progression free survival (PFS) period for patients who received palbociclib in combination with either letrozole or fulvestrant compared to patients who received letrozole or fulvestrant as single agents.
−Removed: These patients had previously progressed on or after prior endocrine therapy.
−Removed: Worldwide sales of currently marketed CDK4/6 inhibitors, which are indicated for the treatment of breast cancer, were $6.0 billion in 2019, and are expected to grow to $14.4 billion in 2026.
−Removed: Worldwide sales of Pfizer’s leading CDK4/6 inhibitor, palbocicib, or Ibrance®, were $5.4 billion in 2020.
−Removed: PI3K inhibitors .
−Removed: Another common mechanism of resistance to endocrine inhibitors is the activation of the PI3K pathway, an important intracellular pathway that regulates cell growth and metabolism.
−Removed: Approximately one third of HR+ breast cancer tumors resistant to endocrine therapy harbor activating mutations of the catalytic subunit of PI3K, referred to as PIK3CA.
−Removed: Fulvestrant used in combination with alpelisib, an oral PI3K-α inhibitor marketed as Piqray® by Novartis approved by the FDA in May 2019, has demonstrated improved clinical efficacy in patients whose tumors had a PIK3CA mutation and had not yet received treatment with a CDK4/6 inhibitor.
−Removed: These patients had previously progressed on or after prior endocrine therapy.
−Removed: Worldwide sales of Piqray®, currently the only FDA-approved for the treatment of breast cancer, limited to patients with PIK3CA mutations, were approximately $320.0 million in 2020.
−Removed: mTOR inhibitors .
−Removed: Similar to CDK4/6 and PI3K, the mTOR pathway has also been identified as a mechanism of resistance to endocrine therapy.
−Removed: Everolimus is an mTOR inhibitor that is currently approved by the FDA for the treatment of HR+/HER2- advanced breast cancer in combination with exemestane, an AI.
−Removed: Everolimus has also shown clinical benefit in combination with fulvestrant.
−Removed: These patients had previously progressed on or after prior AI therapy.
−Removed: Worldwide sales in breast cancer of everolimus, marketed as Afinitor® by Novartis and a leading mTOR inhibitor, were approximately $831.0 million in 2019.
−Removed: The Importance of Targeting PI3K and mTOR in Cancer
−Removed: Activation of the PI3K/mTOR pathway has been implicated in a wide variety of human cancers, involving either activating mutations, or other unknown drivers of pathway amplification.
+Added: Four different classes of targeted therapies are currently used to treat ER+/HER2- tumors - endocrine-based therapies, CDK4/6 inhibitors, PI3K inhibitors and mTOR inhibitors.
+Added: Each of the CDK4/6 inhibitors, PI3K inhibitors and mTOR inhibitors are generally used to respond to the related mechanisms of resistance to endocrine therapy, namely, activation of the CDK4/6, PI3K and mTOR pathways.
+Added: These drugs generated revenues of over $8 billion globally in 2020.
+Added: As specifically relates to gedatolisib, activation of the PI3K/mTOR pathway has been implicated in a wide variety of human cancers, involving either activating mutations, or other unknown drivers of pathway amplification.
These include cancers of the breast, prostate, endometrial, colon, rectum, and lung, among others.
18 unchanged sentences
In cancer, dysfunctional signaling leads to various constitutive activities of mTOR complexes, making mTOR a good therapeutic target.
−Removed: The illustration below depicts the PI3K/AKT/mTOR pathway and various pathway activation mechanisms.
PI3K/mTOR as Resistance Mechanism to Endocrine and CDK4/6 Inhibitors
34 unchanged sentences
The experience with an FDA approved oral p110-α specific inhibitor, Piqray, illustrates the challenge.
−Removed: In its Phase 3 pivotal trial Piqray was found to induce a Grade 3 or 4 adverse event related to hyperglycemia in 39% of patients evaluated.
+Added: In its Phase 3 pivotal trial Piqray was found to induce a Grade 3 or 4 adverse event (AE) related to hyperglycemia in 39% of patients evaluated.
In addition, 26% of patients discontinued treatment.
11 unchanged sentences
At the MTD, the majority of patients enrolled in the MTD group experienced only grade 1 treatment-related adverse events (AEs).
−Removed: Grade 3 treatment-related adverse events were noted in 23.8% of patients, and the most frequently reported included mucosal inflammation and stomatitis (7.1%), increased ALT (7.1%), and increased AST (4.8%).
+Added: Grade 3 treatment-related adverse events were noted in 23.8% of patients, and the most frequently reported included mucosal inflammation and stomatitis (7.1%), increased alternative lengthening of telomeres (ALT) (7.1%), and increased aspartate aminotransferase (AST) (4.8%).
No treatment-related AEs of grade 4 or 5 severity were reported at any dose level.
30 unchanged sentences
For all arms in aggregate, all patients experienced at least one Grade 1 or Grade 2 treatment-emergent adverse event.
−Removed: The most commonly reported adverse events regardless of grade and occurring in at least 30% of patients included stomatitis (81%), neutropenia (80%), nausea (75%), fatigue (68%), dysegeusia (46%), vomiting (45%), anemia (40%), diarrhea (34%), decreased appetite (32%), leukopenia (32%).
+Added: The most commonly reported adverse events regardless of grade and occurring in at least 30% of patients included stomatitis (81%), neutropenia (80%), nausea (75%), fatigue (68%), dysgeusia (46%), vomiting (45%), anemia (40%), diarrhea (34%), decreased appetite (32%), leukopenia (32%).
For all arms in aggregate, the Grade 3 and 4 treatment-emergent adverse events occurring in at least 20% of patients were neutropenia (67%), stomatitis (27%) and rash (20%).
8 unchanged sentences
Gedatolisib was discontinued in 7% of patients.
−Removed: 22 patients were continuing to receive gedatolisib in combination with the other study drugs, 17 of whom have been on study treatment for more than two years.
+Added: As of the cutoff date, 22 patients were continuing to receive gedatolisib in combination with the other study drugs, 17 of whom have been on study treatment for more than two years.
Preliminary best overall response data for each arm is presented in the table below:
41 unchanged sentences
We enacted rigorous safety measures in our laboratory and administrative offices, including implementing social distancing protocols, allowing working from home for those employees that do not need to be physically present in a lab to perform their work, suspending travel, implementing temperature checks at the entrances to our facilities, extensively and frequently disinfecting our workspaces and providing masks to those employees who must be physically present.
−Removed: We expect to continue with these measures until the COVID-19 pandemic is contained and we may take further actions as government authorities require or recommend or as we determine to be in the best interests of our employees, suppliers, and collaborators.
+Added: We expect to continue with these measures until the COVID-19 pandemic is better contained and we may take further actions as government authorities require or recommend or as we determine to be in the best interests of our employees, suppliers, and collaborators.
Clinical Trials and Collaborations
As a result of the COVID-19 pandemic, governmental authorities implemented numerous and constantly evolving measures to try to contain the virus, such as travel bans and restrictions, limits on gatherings, quarantines, shelter-in-place orders, and business shutdowns.
+Added: While many of these measures have been relaxed in recent months, new variants of the coronavirus, such as the delta variant, appear likely to cause new or former protective measures to be reconsidered.
As we continue to advance our clinical trial collaborations, we are in close contact with our current clinical sponsors, and principal investigators, as well as prospective pharmaceutical company and clinical collaborators, to assess the impact of COVID-19 on our trial enrollment timelines and collaboration discussions.
6 unchanged sentences
However, in light of the focus of healthcare providers and hospitals on fighting the virus, several of the clinical sites that provide us tumor tissue for research have halted this service, reducing the number of new tumor tissue specimens we would typically expect to receive.
−Removed: These various constraints may slow or diminish our research and development activities.
−Removed: In addition, cancer research-related industry meetings, such as the American Association for Cancer Research (AACR), were delayed for several months.
−Removed: Our submissions to present research results at these meetings were accepted, but the release of the results were postponed in conjunction with the delayed meeting schedules.
−Removed: Although there is uncertainty related to the anticipated impact of the recent COVID-19 outbreak on our future results, we believe our existing balance of cash and cash equivalents will be sufficient to meet our cash needs arising in the ordinary course of business for at least the next twelve months.
+Added: These various constraints may slow or diminish our research and development activities, particularly if the pandemic continues to experience rising infections from the delta variant of the coronavirus or otherwise.
+Added: In addition, cancer research-related industry meetings, such as the American Association for Cancer Research (AACR), were previously delayed for several months and could be again in the future as a result of the virus.
+Added: So far, our submissions to present research results at these meetings have been accepted, but the release of the results have been postponed in conjunction with the delayed meeting schedules.
+Added: We cannot be certain as to whether these types of delays will continue and what the impact will be on our ability to present research results in the future.
Results of Operations
1 unchanged sentence
As a result, we are not and have never been profitable and have incurred losses in each period since our inception in 2012.
−Removed: For the three months ended March 31, 2021 and 2020, we reported a net loss of approximately $2.8 million and $2.2 million, respectively.
−Removed: As of March 31, 2021, we had an accumulated deficit of approximately $12.6 million under Celcuity LLC and $29.1 million under Celcuity Inc.
−Removed: As of March 31, 2021, we had cash and cash equivalents of approximately $34.9 million.
+Added: For the three months ended June 30, 2021 and 2020, we reported a net loss of approximately $14.0 million and $2.2 million, respectively, and for the six months ended June 30, 2021 and 2020, we reported a net loss of approximately $16.8 million and $4.4 million, respectively.
+Added: As of June 30, 2021, we had an accumulated deficit of approximately $43.1 million.
+Added: As of June 30, 2021, we had cash and cash equivalents of approximately $41.6 million.
Components of Operating Results
19 unchanged sentences
General and administrative expenses consist primarily of salaries, benefits and stock-based compensation related to our executive, finance and support functions.
−Removed: Other general and administrative expenses include professional fees for auditing, tax, and legal services associated with being a public company, director and officer insurance and travel expenses for our general and administrative personnel.
+Added: Other general and administrative expenses include professional fees for auditing, tax, and legal services associated with being a public company, director and officer insurance, investor relations and travel expenses for our general and administrative personnel.
Sales and Marketing
4 unchanged sentences
Interest Expense
−Removed: Interest expense is the result of finance lease obligations.
+Added: Interest expense is primarily due to a loan agreement and finance lease obligations.
Interest Income
10 unchanged sentences
Loss from operations
+Added: (13,643,468 )
+Added: (11,429,527 )
Other income (expense)
2 unchanged sentences
Loss on sale of fixed assets
−Removed: Other income, net
+Added: Other income (expense), net
Net loss before income taxes
+Added: (14,032,852 )
+Added: (11,830,863 )
Income tax benefits
1 unchanged sentence
$ (2,201,989 )
+Added: $ (11,830,863 )
+Added: Six Months Ended
+Added: Increase (Decrease)
+Added: Percent Change
+Added: Statements of Operations Data:
+Added: Operating expenses:
Research and development
−Removed: Our research and development expenses for the three months ended March 31, 2021 were approximately $2.24 million, representing an increase of approximately $0.39 million, or 21%, compared to the same period in 2020.
−Removed: The increase primarily resulted from a $0.06 million increase in compensation related expenses, which included a decrease of approximately $0.04 million of non-cash stock-based compensation, to support development of our CELsignia platform.
−Removed: In addition, other research and development expenses increased $0.33 million due to clinical validation and laboratory studies, and operational and business development activities.
+Added: General and administrative
+Added: Total operating expenses
+Added: Loss from operations
+Added: (16,435,238 )
+Added: (11,910,484 )
+Added: Other income (expense)
+Added: Interest expense
+Added: Interest income
+Added: Gain on sale of fixed assets
+Added: Other income (expense), net
+Added: Net loss before income taxes
+Added: (16,824,520 )
+Added: (12,375,536 )
+Added: Income tax benefits
+Added: $ (16,824,520 )
+Added: $ (4,448,984 )
+Added: $ (12,375,536 )
+Added: Research and Development
+Added: Our research and development expenses for the three months ended June 30, 2021 were approximately $13.07 million, representing an increase of approximately $11.30 million, or 640%, compared to the same period in 2020.
+Added: The increase primarily resulted from a $10.0 million upfront license fee related to the execution of the Pfizer license agreement, which included $5.0 million of non-cash expense for the issuance of common stock.
+Added: Compensation related expenses accounted for a $0.61 million increase, including approximately $0.06 million of non-cash stock-based compensation, to support development of our CELsignia platform and the development of gedatolisib.
+Added: In addition, other research and development expenses increased $0.69 million due to clinical validation and laboratory studies, legal fees related to patent prosecution and operational and business development activities.
+Added: Our research and development expenses for the six months ended June 30, 2021 were approximately $15.31 million, representing an increase of approximately $11.69 million, or 324%, compared to the same period in 2020.
+Added: The increase primarily resulted from a $10.0 million upfront license fee related to the execution of the Pfizer license agreement, which included $5.0 million of non-cash expense for the issuance of common stock.
+Added: Compensation related expenses accounted for a $0.71 million increase, including approximately $0.03 million of non-cash stock-based compensation, to support development of our CELsignia platform and the development of gedatolisib.
+Added: In addition, other research and development expenses increased $0.98 million due to clinical validation and laboratory studies, legal fees related to patent prosecution and operational and business development activities.
Conducting a significant amount of research and development is central to our business model.
We plan to increase our research and development expenses for the foreseeable future as we seek to discover new cancer sub-types, develop and validate additional CELsignia tests to diagnose such sub-types and develop gedatolisib.
−Removed: We also expect to incur increased expenses to support companion diagnostic business development activities with pharmaceutical companies as we develop additional CELsignia tests.
+Added: We also expect to incur increased expenses to support companion diagnostic business development activities with pharmaceutical companies as we develop additional CELsignia tests and initiate a clinical trial for gedatolisib.
General and Administrative
−Removed: Our general and administrative expenses for the three months ended March 31, 2021 were approximately $0.56 million, representing an increase of approximately $0.09 million, or 20%, compared to the same period in 2020.
−Removed: The increase primarily resulted from a $0.08 million increase in professional fees associated with being a public company and director and officer insurance.
−Removed: We anticipate that our general and administrative expenses will increase in future periods, reflecting both increased costs in connection with the potential future commercialization of CELsignia tests, an expanding infrastructure, and increased professional fees associated with being a public company.
+Added: Our general and administrative expenses for the three months ended June 30, 2021 were approximately $0.57 million, representing an increase of approximately $0.13 million, or 28%, compared to the same period in 2020.
+Added: The increase primarily resulted from a $0.05 million increase in non-cash stock-based compensation.
+Added: In addition, other general and administrative expenses increased $0.08 million due to professional fees associated with being a public company and director and officer insurance.
+Added: Our general and administrative expenses for the six months ended June 30, 2021 were approximately $1.13 million, representing an increase of approximately $0.22 million, or 24%, compared to the same period in 2020.
+Added: The increase primarily resulted from a $0.08 million increase in non-cash stock-based compensation.
+Added: In addition, other general and administrative expenses increased $0.14 million due to professional fees associated with being a public company and director and officer insurance.
+Added: We anticipate that our general and administrative expenses will increase in future periods, reflecting both increased costs in connection with the potential future commercialization of CELsignia tests and gedatolisib, an expanding infrastructure, and increased professional fees associated with being a public company.
Interest Expense
−Removed: Interest expense for the three months ended March 31, 2021 is related to finance lease liabilities.
+Added: Interest expense for the three months and six months ended June 30, 2021 was $0.4 million and represents an increase of $0.4 million compared to the same periods in 2020.
+Added: The increase is due to the loan agreement that was executed in April 2021 and includes $0.17 million of non-cash interest expense.
Interest Income
−Removed: Interest income for the three months ended March 31, 2021 was minimal and represents a decrease of approximately $0.06 million or 99% compared to the same period in 2020.
+Added: Interest income for the three months and six months ended June 30, 2021 represents a decrease of approximately $0.01 and $0.07 million, respectively, compared to the same period in 2020.
This decrease was primarily the result of lower market interest rates.
1 unchanged sentence
Since our inception, we have incurred losses and cumulative negative cash flows from operations.
−Removed: Through March 31, 2021, we have raised capital of approximately $13.7 million and $7.5 million through private placements of common equity and unsecured convertible notes, respectively.
+Added: Through June 30, 2021, we have raised capital of approximately $13.7 million and $7.5 million through private placements of common equity and unsecured convertible notes, respectively.
On September 22, 2017, we closed on the initial public offering of our common stock, which generated approximately $23.3 million of additional cash after taking into account underwriting discounts and commissions and offering expenses.
2 unchanged sentences
The ATM Agreement allowed us to sell shares of common stock up to an aggregate offering price of $10.0 million.
−Removed: Through March 31, 2021, we generated approximately $0.09 million of additional cash through sales pursuant to the ATM Agreement, after taking into account commissions and offering expenses.
+Added: Through June 30, 2021, we generated approximately $0.09 million of additional cash through sales pursuant to the ATM Agreement, after taking into account commissions and offering expenses.
On February 26, 2021, we completed a follow-on offering of our common stock, which generated approximately $25.8 million of additional cash after taking into account underwriting discounts and offering expenses.
In conjunction with the follow-on offering, the ATM Agreement was terminated.
+Added: On April 8, 2021, we entered into a loan agreement with Innovatus Life Sciences Lending Fund I, LP (“Innovatus”), whereby Innovatus agreed to loan up to $25 million in three tranches consisting of (i) a $15.0 million non-contingent term A loan that was funded on April 8, 2021, (ii) a $5 million term B loan to be funded upon our request no later than March 31, 2022, and (iii) a $5 million term C loan to be funded upon our request no later than March 31, 2023.
+Added: Funding of the term B and C loan is subject to our ability to achieve certain milestones.
Cash from these capital raising activities has been our primary source of funds for our operations since inception.
−Removed: As of March 31, 2021, our cash and cash equivalents were approximately $34.9 million, and we had an accumulated deficit of approximately $12.6 million under Celcuity LLC and approximately $29.1 million under Celcuity Inc.
+Added: As of June 30, 2021, our cash and cash equivalents were approximately $41.6 million, and we had an accumulated deficit of approximately $43.1 million.
+Added: Our cash and cash equivalents does not include the proceeds of a follow-on offering that we completed on July 1, 2021, whereby we generated gross proceeds of approximately $56.3 million before deducting underwriting discounts of approximately $3.4 million and offering expenses of approximately $0.1 million.
We expect that our research and development and general and administrative expenses will increase as we continue to develop our CELsignia platform and additional CELsignia tests, conduct research related to the discovery of new cancer sub-types, conduct clinical trials, develop gedatolisib and pursue other business development activities.
7 unchanged sentences
Additional capital may not be available on reasonable terms, or at all.
−Removed: Three Months Ended
+Added: Six Months Ended
Net cash provided by (used in):
7 unchanged sentences
Operating Activities
−Removed: Net cash used in operating activities was approximately $2.52 million for the three months ended March 31, 2021 and consisted primarily of a net loss of approximately $2.79 million and working capital changes of approximately $0.28 million, adjusted for non-cash expense items of approximately $0.55 million.
−Removed: The approximately $0.28 million of working capital changes was primarily due to an increase in prepaid assets and a decrease in accrued expenses.
−Removed: Non-cash expense items of approximately $0.55 million primarily consisted of depreciation expense of $0.10 million and $0.45 million of stock-based compensation expense.
−Removed: The net cash used in operating activities was approximately $1.83 million for the three months ended March 31, 2020 and consisted primarily of a net loss of approximately $2.25 million and working capital changes of approximately $0.14 million, offset by non-cash expense items of approximately $0.56 million.
−Removed: The approximately $0.14 million of working capital changes was primarily due to an increase in prepaid assets and decreases in accounts payable.
−Removed: Non-cash expense items of approximately $0.56 million primarily consisted of depreciation expense of $0.10 million and stock-based compensation expense of approximately $0.46 million.
+Added: Net cash used in operating activities was approximately $10.14 million for the six months ended June 30, 2021 and consisted primarily of a net loss of approximately $16.82 million, offset by non-cash expense items of approximately $6.34 million and working capital changes of $0.34 million.
+Added: Non-cash expense items of approximately $6.34 million primarily consisted of $5.0 million for issuance of common stock related to a license agreement, $0.99 million of stock-based compensation expense, depreciation expense of $0.18 million and non-cash interest expense of $0.17 million.
+Added: The approximately $0.34 million of working capital changes was primarily due to an increase in accounts payable and a decrease in accrued expenses.
+Added: The net cash used in operating activities was approximately $3.39 million for the six months ended June 30, 2020 and consisted primarily of a net loss of approximately $4.45 million and working capital changes of approximately $0.02 million, offset by non-cash expense items of approximately $1.08 million.
+Added: Non-cash expense items of approximately $1.08 million primarily consisted of $0.89 million of stock-based compensation expense and depreciation expense of $0.19 million.
Investing Activities
−Removed: Net cash used in investing activities for the three months ended March 31, 2021 was approximately $0.03 million and consisted of purchases of property and equipment.
−Removed: Net cash used in investing activities for the three months ended March 31, 2020 was approximately $0.05 million and consisted of purchases of property and equipment.
+Added: Net cash used in investing activities for the six months ended June 30, 2021 was approximately $0.06 million and consisted of purchases of property and equipment.
+Added: Net cash used in investing activities for the six months ended June 30, 2020 was approximately $0.07 million and consisted of purchases of property and equipment.
Financing Activities
−Removed: Net cash provided by financing activities for the three months ended March 31, 2021 was approximately $25.85 million and primarily reflects net proceeds from the sale of shares of our common stock through a follow-on offering.
−Removed: The net cash used by financing activities for the three months ended March 31, 2020 was minimal and primarily reflects payments for finance leases.
+Added: Net cash provided by financing activities for the six months ended June 30, 2021 was approximately $40.20 million.
+Added: The $40.20 million primarily consisted of $25.77 million from net proceeds from the sale of shares of our common stock through a follow-on offering and $14.35 million from net proceeds related to the closing of a loan agreement.
+Added: The remaining $0.08 million was the result of proceeds from the exercise of common stock warrants and employee stock options and proceeds from employee stock purchases.
+Added: The net cash used by financing activities for the six months ended June 30, 2020 was approximately $0.15 million and primarily reflects net proceeds from the sale of shares of our common stock through the ATM Agreement and employee stock purchases.
Off-Balance Sheet Arrangements
58 unchanged sentences
Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.