On August 9, 2022 Intra-Cellular Therapies, Inc. (Nasdaq: ITCI), a biopharmaceutical company focused on the development and commercialization of therapeutics for central nervous system (CNS) disorders, reported its financial results for the second quarter ended June 30, 2022 and provided a corporate update (Press release, Intra-Cellular Therapies, AUG 9, 2022, View Source [SID1234617901]).

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"In this quarter, CAPLYTA experienced significant revenue growth, increasing nearly 60% over the first quarter of 2022, driven by strong uptake in bipolar depression. We expect to continue to deliver strong revenue growth throughout 2022 and also look forward to advancing our development programs," said Dr. Sharon Mates, Chairman and CEO of Intra-Cellular Therapies.

SECOND QUARTER FINANCIAL HIGHLIGHTS

Total revenues were $55.6 million for the second quarter of 2022, compared to $20.0 million for the second quarter of 2021. Net product revenues of CAPLYTA were $55.1 million for the second quarter of 2022, compared to $19.0 million for the same period in 2021, representing a year-over-year increase of 190% and a 58% increase over the first quarter of 2022.
Cost of product sales were $4.7 million in the second quarter of 2022, compared to $2.0 million for the second quarter of 2021.
Selling, general and administrative (SG&A) expenses were $100.3 million for the second quarter of 2022, compared to $69.9 million for the second quarter of 2021. This increase is primarily due to an increase in marketing and advertising expenses and labor related costs.
Research and development (R&D) expenses for the second quarter of 2022 were $38.5 million, compared to $17.3 million for the second quarter of 2021. This increase is due to higher lumateperone clinical trial and non-clinical related costs and an increase in non-lumateperone project costs.
Net loss for the quarter ended June 30, 2022 was $86.6 million, compared to a net loss of $68.7 million for the quarter ended June 30, 2021.
Cash, cash equivalents, restricted cash and investment securities totaled $679.2 million at June 30, 2022, compared to $413.7 million at December 31, 2021. In January 2022, the Company completed a $460.0 million public offering resulting in net proceeds to the Company of approximately $433.7 million from the sale of 10,952,381 shares of its common stock, after deducting underwriting discounts and commissions and offering expenses.
COMMERCIAL HIGHLIGHTS

Q2 2022 marks the second full quarter of the launch of the CAPLYTA’s bipolar depression indication following U.S. Food and Drug Administration (FDA) approval in late December 2021. CAPLYTA is the first and only FDA-approved treatment for depressive episodes associated with bipolar I or II disorder (bipolar depression) in adults as monotherapy and as adjunctive therapy with lithium or valproate.
The significant launch inflection continued in both new and total prescriptions, reflecting sustained robust growth following approval in bipolar depression. Second quarter CAPLYTA new and total prescriptions increased by 55% and 51%, respectively, versus the first quarter of 2022. Second quarter CAPLYTA new and total prescriptions increased by 225% and 191%, respectively, versus the second quarter of 2021.
Following FDA approval during the second quarter of 2022, two new dosage strengths of CAPLYTA, 10.5 mg and 21 mg, are expected to be available in pharmacies this month. This will expand the patient population who has access to CAPLYTA, specifically for patients taking strong or moderate CYP3A4 inhibitors and patients with moderate or severe hepatic impairment.
CAPLYTA maintained broad coverage in the Medicare Part D and Medicaid channels, with greater than 98% of lives covered and, during the quarter, we further expanded coverage in the Commercial channel to approximately 85% of lives covered. Our LytaLink patient support program continues to be highly effective in supporting patient access.
CLINICAL HIGHLIGHTS

Lumateperone:

Mixed Features program: Patient enrollment is progressing well in Study 403, a global clinical trial evaluating lumateperone 42 mg in patients with major depressive disorder (MDD) and in patients with bipolar depression who exhibit mixed features. The primary endpoint is change from baseline versus placebo on the MADRS total score at week 6, and the CGI-S scale is the key secondary endpoint. We expect to complete clinical conduct in this study in late 2022.
Adjunctive MDD program: Patient enrollment in pivotal global studies 501 and 502 evaluating lumateperone 42 mg as adjunctive treatment to anti-depressants is ongoing. We expect to file a supplemental New Drug Application (sNDA) with the FDA for lumateperone as an adjunctive therapy to antidepressants for the treatment of MDD in 2024.
Presentations: In the second quarter of 2022, there were lumateperone research presentations at the American Psychiatric Association (APA) Meeting, the International Conference for Bipolar Disorders (ISBD) Annual Meeting, the American Society of Clinical Psychopharmacology (ASCP), and the Schizophrenia International Research Society (SIRS). The presentations included additional analyses from our lumateperone bipolar depression program including findings consistent with broad antidepressant effects, marked improvements in patients’ daily functioning, and further evidence of a favorable metabolic profile.

At SIRS, we presented safety analyses from our open-label safety switching study evaluating lumateperone 42 mg in patients with stable schizophrenia. Overall, data from this post-hoc analysis further support the favorable safety and tolerability profile of lumateperone 42 mg in patients with schizophrenia who switched from another antipsychotic, irrespective of the previous antipsychotic. In addition, patients switching from risperidone/paliperidone or olanzapine to lumateperone had significant improvements in cardiometabolic parameters and prolactin concentrations.
Lumateperone Long Acting Injectable (LAI) formulation: We have completed the preclinical development of an LAI formulation, and we have conducted a Phase 1 single ascending dose study with this formulation. This study evaluated the pharmacokinetics, safety and tolerability of lumateperone LAI in patients with stable symptoms of schizophrenia. We are exploring alternate sites of injection with this formulation as well as progressing other formulations. This will assist us in evaluating dosing strategies and formulation for our efficacy studies. The goal of our program is to develop LAI formulations that are effective, safe and well-tolerated with treatment durations of one month and longer.
Other Programs:

ITI-1284-ODT-SL program: ITI-1284 is a deuterated form of lumateperone, a new chemical entity formulated as an oral disintegrating tablet for sublingual administration. We are presently evaluating ITI-1284-ODT-SL in Phase 1 studies including drug-drug interaction studies. We expect to commence clinical conduct in Phase 2 clinical trials in agitation in patients with probable Alzheimer’s disease, in dementia-related psychosis and certain depressive disorders in the elderly in 2023.
Phosphodiesterase type I inhibitor (PDE1) program: We have initiated our Phase 2 clinical program with lenrispodun for Parkinson’s disease and expect to commence patient enrollment in the second half of 2022.

We continue to investigate the anti-cancer effects of PDE1 inhibitors. In April of this year, we presented preclinical data at the AACR (Free AACR Whitepaper) Annual meeting describing the antitumor effects of PDE1 inhibitors, when administered in conjunction with checkpoint inhibitor immunotherapy in an animal model of triple negative breast cancer. We have now shown that our PDE1 inhibitors can potentiate the action of checkpoint inhibitors in various models of colorectal, kidney, breast and glioblastoma cancers. We plan to present additional data from this program at future scientific meetings.
ITI-333 program in Opioid Use Disorder: We continue to advance the development of ITI-333. Following the recent completion of our single ascending dose study, we have commenced a neuroimaging study to investigate brain occupancy for receptors that play a role in substance use disorder and also have applicability for pain. The results of this study will support the dose selection for future studies.
Conference Call and Webcast Details

The Company will host a live conference call and webcast today at 8:30 AM Eastern Time to discuss the Company’s financial results and provide a corporate update. The live webcast and subsequent replay may be accessed by visiting the Company’s website at www.intracellulartherapies.com. Please connect to the Company’s website at least 5-10 minutes prior to the live webcast to ensure adequate time for any necessary software download. Alternatively, please call 1-(877) 407-8291 (U.S.) or 1-(201) 689-8345 (international) to listen to the live conference call. Please dial in approximately 10 minutes prior to the call.

CAPLYTA (lumateperone) is indicated in adults for the treatment of schizophrenia and depressive episodes associated with bipolar I or II disorder (bipolar depression) as monotherapy and as adjunctive therapy with lithium or valproate.

Important Safety Information

Boxed Warnings:

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. CAPLYTA is not approved for the treatment of patients with dementia-related psychosis.
Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adults in short-term studies. All antidepressant-treated patients should be closely monitored for clinical worsening, and for emergence of suicidal thoughts and behaviors. The safety and effectiveness of CAPLYTA have not been established in pediatric patients.
Contraindications: CAPLYTA is contraindicated in patients with known hypersensitivity to lumateperone or any components of CAPLYTA. Reactions have included pruritus, rash (e.g., allergic dermatitis, papular rash, and generalized rash), and urticaria.

Warnings & Precautions: Antipsychotic drugs have been reported to cause:

Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis, including stroke and transient ischemic attack. See Boxed Warning above.
Neuroleptic Malignant Syndrome (NMS), which is a potentially fatal reaction. Signs and symptoms include: high fever, stiff muscles, confusion, changes in breathing, heart rate, and blood pressure, elevated creatinine phosphokinase, myoglobinuria (and/or rhabdomyolysis), and acute renal failure. Patients who experience signs and symptoms of NMS should immediately contact their doctor or go to the emergency room.
Tardive Dyskinesia, a syndrome of uncontrolled body movements in the face, tongue, or other body parts, which may increase with duration of treatment and total cumulative dose. TD may not go away, even if CAPLYTA is discontinued. It can also occur after CAPLYTA is discontinued.
Metabolic Changes, including hyperglycemia, diabetes mellitus, dyslipidemia, and weight gain. Hyperglycemia, in some cases extreme and associated with ketoacidosis, hyperosmolar coma or death, has been reported in patients treated with antipsychotics. Measure weight and assess fasting plasma glucose and lipids when initiating CAPLYTA and monitor periodically during long-term treatment.
Leukopenia, Neutropenia, and Agranulocytosis (including fatal cases). Complete blood counts should be performed in patients with pre-existing low white blood cell count (WBC) or history of leukopenia or neutropenia. CAPLYTA should be discontinued if clinically significant decline in WBC occurs in absence of other causative factors.
Decreased Blood Pressure & Dizziness. Patients may feel lightheaded, dizzy or faint when they rise too quickly from a sitting or lying position (orthostatic hypotension). Heart rate and blood pressure should be monitored and patients should be warned with known cardiovascular or cerebrovascular disease. Orthostatic vital signs should be monitored in patients who are vulnerable to hypotension.
Falls. CAPLYTA may cause sleepiness or dizziness and can slow thinking and motor skills, which may lead to falls and, consequently, fractures and other injuries. Patients should be assessed for risk when using CAPLYTA.
Seizures. CAPLYTA should be used cautiously in patients with a history of seizures or with conditions that lower seizure threshold.
Potential for Cognitive and Motor Impairment. Patients should use caution when operating machinery or motor vehicles until they know how CAPLYTA affects them.
Body Temperature Dysregulation. CAPLYTA should be used with caution in patients who may experience conditions that may increase core body temperature such as strenuous exercise, extreme heat, dehydration, or concomitant anticholinergics.
Dysphagia. CAPLYTA should be used with caution in patients at risk for aspiration.

Drug Interactions: CAPLYTA should not be used with CYP3A4 inducers. Dose reduction is recommended for concomitant use with strong CYP3A4 inhibitors or moderate CYP3A4 inhibitors.

Special Populations: Newborn infants exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. Breastfeeding is not recommended. Dose reduction is recommended for patients with moderate or severe hepatic impairment.

Adverse Reactions: The most common adverse reactions in clinical trials with CAPLYTA vs. placebo were somnolence/sedation, dizziness, nausea, and dry mouth.

Please click here to see full Prescribing Information including Boxed Warning.

About CAPLYTA (lumateperone)

CAPLYTA 42 mg is an oral, once daily atypical antipsychotic approved in adults for the treatment of schizophrenia and depressive episodes associated with bipolar I or II disorder (bipolar depression) as monotherapy and as adjunctive therapy with lithium or valproate. While the mechanism of action of CAPLYTA is unknown, the efficacy of CAPLYTA could be mediated through a combination of antagonist activity at central serotonin 5-HT2A receptors and postsynaptic antagonist activity at central dopamine D2 receptors.

Lumateperone is being studied for the treatment of major depressive disorder, and other neuropsychiatric and neurological disorders. Lumateperone is not FDA-approved for these disorders.

On August 9, 2022 Xilio Therapeutics, Inc. (Nasdaq: XLO), a biotechnology company developing tumor-selective immuno-oncology therapies for people living with cancer, reported pipeline and business updates and reported financial results for the second quarter ended June 30, 2022 (Press release, Xilio Therapeutics, AUG 9, 2022, View Source [SID1234617900]).

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"We are encouraged by the preliminary dose-escalation data reported today for XTX101, a tumor-selective anti-CTLA-4. These data provide initial clinical validation of Xilio’s geographically precise solutions (GPS) platform and demonstrate that XTX101 has reached dose levels above the target dose with limited active (unmasked) molecule in peripheral circulation. Based on these data, we plan to explore a Phase 2 clinical trial for XTX101 in microsatellite stable (MSS) colorectal cancer," said René Russo, Pharm.D., chief executive officer of Xilio. "With a strong balance sheet and experienced leadership team, we are well-positioned to continue to advance our pipeline and anticipate multiple clinical data milestones for XTX101 and XTX202 in 2023."

XTX101: Preliminary Dose-Escalation Data from Ongoing Phase 1 Clinical Trial

XTX101, an Fc-enhanced, tumor-selective anti-CTLA-4, is being evaluated in a Phase 1 clinical trial in patients with advanced solid tumors. The target dose level for XTX101 of 60 mg is anticipated to provide anti-tumor activity similar to ipilimumab at 10 mg/kg (approximately 600 mg in a 60 kg patient) based on the 10 times greater potency observed for XTX101 relative to an ipilimumab analogue in preclinical studies.

As of August 5, 2022, 12 patients have been treated with XTX101 in the monotherapy dose-escalation cohort (Part 1A) at four dose levels ranging from 7 mg to 180 mg:

The 180 mg dose level has surpassed the 60 mg target dose level for XTX101. As a result, Xilio recently expanded enrollment at the 180 mg dose level.
A maximum tolerated dose (MTD) has not yet been determined, and enrollment in the dose-escalation cohort is ongoing.
Preliminary pharmacokinetic (PK) analyses demonstrated dose-proportional drug exposure, with limited active (unmasked) XTX101 in peripheral circulation (range of % active in periphery: 6% – 16%) consistent with PK data observed in preclinical studies.
Additional XTX101 Development Updates

Xilio recently opened Part 1B of the clinical trial for patient enrollment, which is a monotherapy cohort designed to evaluate anti-tumor activity, including intra-tumoral PK and pharmacodynamic (PD) data, in patients with anti-CTLA-4 sensitive tumor types, with the goal of characterizing the anti-tumor activity of XTX101 at one or more dose levels selected in Part 1A of the trial.
Given the potential for Fc-enhanced anti-CTLA-4 agents like XTX101 to demonstrate activity in tumors that are historically resistant to immuno-oncology treatment, Xilio plans to explore evaluating XTX101 in a Phase 2 clinical trial in patients with microsatellite stable (MSS) colorectal cancer in combination with an anti-PD(L)-1.
XTX202: Phase 1 Clinical Trial Progress

XTX202, a tumor-selective, engineered IL-2, is being evaluated in a Phase 1 clinical trial in patients with advanced solid tumors. As of August 5, 2022, six patients have been treated with XTX202 as outpatients in the monotherapy dose-escalation cohort (Part 1A) at three dose levels ranging from 0.27 mg/kg to 0.53 mg/kg. An MTD has not yet been determined, and enrollment in the dose-escalation cohort is ongoing.

Upcoming Anticipated Milestones

Xilio anticipates multiple milestones through the end of 2023:

XTX101

Report data from Part 1A of the trial (monotherapy dose-escalation cohort) supporting the recommended Phase 2 dose (RP2D) in the first half of 2023. Xilio anticipates the data for Part 1A will include available safety and anti-tumor activity, as well as peripheral PK and PD data.
Report preliminary data from Part 1B of the trial (monotherapy expansion cohort) in the middle of 2023. Xilio anticipates the data for Part 1B will include available safety and anti-tumor activity, as well as intra-tumoral PK and PD data.
Initiate patient enrollment in Part 1C of the trial (pembrolizumab combination cohort) in the fourth quarter of 2022.
Report preliminary data from Part 1C of the trial in the first half of 2023. Xilio anticipates the data will include available safety and anti-tumor activity, as well as peripheral PK and PD data for XTX101 in combination with pembrolizumab.
XTX202

Report data from Part 1A of the trial (monotherapy dose-escalation cohort) supporting the RP2D in the first half of 2023. Xilio anticipates the data will include available safety and anti-tumor activity, as well as peripheral PK and PD data.
Initiate patient enrollment in Part 1B (monotherapy expansion cohort) in the fourth quarter of 2022. Part 1B is a monotherapy cohort designed to evaluate anti-tumor activity of XTX202 in a basket of indications potentially sensitive to IL-2.
Report preliminary data from Part 1B of the trial (monotherapy expansion cohort) in the second half of 2023. Xilio anticipates the data will include available safety and anti-tumor activity data.
Following the determination of a RP2D, Xilio anticipates initiating a Phase 2 monotherapy trial in the first half of 2023 designed to evaluate the safety and efficacy of XTX202 in patients with melanoma and renal cell carcinoma (RCC). Xilio anticipates enrolling a total of approximately 35 patients across both cohorts in the Phase 2 clinical trial.
XTX301

Submit an investigational new drug application (IND) to the U.S. Food and Drug Administration (FDA) for XTX301 in the fourth quarter of 2022.
Subject to FDA clearance of the IND, Xilio plans to initiate a Phase 1 clinical trial in the first half of 2023 evaluating the safety and tolerability of XTX301 as a monotherapy in patients with advanced solid tumors. The Phase 1 clinical trial will consist of a monotherapy dose-escalation cohort with the goal of determining a RP2D for XTX301 and monotherapy expansion cohorts at the RP2D.
Corporate Highlights

Today, Xilio announced the promotions of Uli Bialucha, Ph.D., to chief scientific officer and Chris Frankenfield to chief legal and administrative officer, each effective as of August 8, 2022. Dr. Bialucha previously served as the company’s senior vice president of research since April 2021, and Mr. Frankenfield previously served as the company’s general counsel since March 2021.
In June 2022, Xilio announced the promotion of Martin Huber, M.D., to president, the election of Paul Clancy as chair of the board of directors, and the appointment of Robert Ross, M.D., as a member of the board of directors.
In May 2022, Xilio announced the appointment of Stacey Davis as chief business officer.
Second Quarter 2022 Financial Results

Cash Position: Cash and cash equivalents were $159.4 million as of June 30, 2022, compared to $198.1 million as of December 31, 2021.
Research & Development (R&D) Expenses: R&D expenses were $16.2 million for the second quarter of 2022, compared to $17.7 million for the second quarter of 2021. The decrease was primarily driven by decreased costs associated with XTX202 manufacturing and preclinical activities, partially offset by increased costs associated with XTX301, as well as higher personnel-related costs mainly due to increased headcount, including a $0.3 million increase in non-cash equity-based compensation expense.
General & Administrative (G&A) Expenses: G&A expenses were $8.3 million for the second quarter of 2022, compared to $5.3 million for the second quarter of 2021. The increase was primarily driven by higher personnel-related costs, primarily due to increased headcount and a $1.4 million increase in non-cash equity-based compensation expense, as well as certain costs related to operating as a publicly traded company.
Net Loss: Net loss was $24.6 million for the second quarter of 2022, compared to $23.2 million for the second quarter of 2021.
Financial Guidance

Xilio continues to anticipate that its existing cash and cash equivalents will be sufficient to fund its operating expenses and capital expenditure requirements into the first half of 2024.

About the Phase 1 Clinical Trial for XTX101

XTX101 is an investigational Fc-enhanced, tumor-selective anti-CTLA-4 monoclonal antibody designed to deplete regulatory T cells when activated selectively (unmasked) in the tumor microenvironment (TME). The Phase 1 clinical trial is a first-in-human, multi-center, open-label trial designed to evaluate the safety and tolerability of XTX101 as a monotherapy, as well as a combination therapy with pembrolizumab, for the treatment of adult patients with advanced solid tumors. The Phase 1 portion of the trial consists of three cohorts. The first cohort (Part 1A) is an accelerated and standard 3+3 dose-escalation monotherapy cohort designed to assess the tolerability of XTX101 in patients with advanced solid tumors who have progressed after receiving the standard-of-care treatment for their tumor. The second cohort (Part 1B) is a monotherapy cohort designed to evaluate evidence of anti-CTLA-4 pharmacodynamic activity in patients who have progressed on anti-PD-1 or anti-PD-L1 treatment but have not received prior treatment with an anti-CTLA-4 therapy. The third cohort (Part 1C) is a combination therapy cohort designed to evaluate XTX101 in combination with pembrolizumab in patients who have not previously been treated with an anti-PD-1 or anti-PD-L1 treatment. The Phase 1 clinical trial is designed to enroll a total of up to approximately 104 patients across all cohorts at multiple sites in the United States. Please refer to NCT04896697 on www.clinicaltrials.gov for additional details.

In May 2021, Xilio entered into a clinical trial collaboration and supply agreement with Merck & Co., Inc. (known as MSD outside the US and Canada) to explore the therapeutic potential of XTX101 in combination with pembrolizumab in patients with advanced solid tumors.

About the Phase 1 Clinical Trial for XTX202

XTX202 is an investigational tumor-selective beta-gamma biased (non-alpha), engineered IL-2 molecule designed to potently stimulate CD8 and natural killer (NK) cells without concomitant stimulation of regulatory T cells when activated selectively (unmasked) in the TME. The Phase 1 clinical trial is a first-in-human, multi-center, open-label trial designed to evaluate the safety and tolerability of XTX202 as a monotherapy in patients with advanced solid tumors. The Phase 1 clinical trial is designed to enroll a total of up to approximately 48 patients across all cohorts at multiple sites in the United States. Please refer to NCT05052268 on www.clinicaltrials.gov for additional details.

About XTX301

XTX301 is an investigational tumor-selective, engineered IL-12 designed to potently stimulate anti-tumor immunity and reprogram the TME of poorly immunogenic "cold" tumors towards an inflamed, or "hot," state. IL-12 plays a key role in bridging innate and adaptive cellular immunity, making it a compelling target for immunotherapy. However, dose-limiting toxicities observed with systemically active IL-12, including life-threatening liver toxicity, have limited the therapeutic potential of IL-12 agents to date. Preclinical studies using a murine surrogate molecule for XTX301 demonstrated in vivo anti-tumor activity at doses as low as 0.04 mg/kg and favorable tolerability. Xilio has completed GLP toxicology studies for XTX301.

On August 9, 2022 Daiichi Sankyo reported that Initial results from the TROPION-Lung02 phase 1b trial showed that datopotamab deruxtecan (Dato-DXd) in combination with pembrolizumab with or without platinum chemotherapy demonstrated promising clinical activity and a tolerable safety profile in patients with previously untreated or pretreated advanced or metastatic non-small cell lung cancer (NSCLC) without actionable genomic alterations. Results were presented today during a late-breaking mini-oral presentation (#MA13.07) at the IASLC 2022 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer (#WCLC22) (Press release, Daiichi Sankyo, AUG 9, 2022, View Source [SID1234617899]).

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Datopotamab deruxtecan is a specifically designed TROP2 directed DXd antibody drug conjugate (ADC) being jointly developed by Daiichi Sankyo (TSE:4568) and AstraZeneca (LSE/STO/Nasdaq: AZN).

NSCLC is diagnosed at an advanced stage in nearly 50% of patients and often has a poor prognosis with worsening outcomes after each line of subsequent therapy.1,2,3 While first-line treatment consisting of immunotherapy with or without chemotherapy has improved outcomes in patients with NSCLC without actionable genomic alterations, disease progression still occurs in the majority of patients and additional treatment strategies in this setting are needed.4,5

An interim analysis of the ongoing TROPION-Lung02 trial in patients with previously untreated or pretreated advanced or metastatic NSCLC without actionable genomic alterations demonstrated a promising overall response rate (ORR) in the overall population of 37% (median follow-up of 6.5 months) of 38 patients receiving datopotamab deruxtecan in combination with pembrolizumab (doublet therapy) and an ORR of 41% (median follow-up of 4.4 months) of 37 patients receiving datopotamab deruxtecan in combination with pembrolizumab and platinum chemotherapy (triplet therapy). A disease control rate (DCR) of 84% was seen with both the doublet and triplet combination therapy in the overall population that comprised both first-line and second-line settings.

In previously untreated patients, ORRs of 62% (eight of the 13 patients receiving doublet therapy) and 50% (10 of 20 patients receiving triplet therapy) were observed. Eight partial responses (PRs) were seen in patients receiving doublet therapy and 10 PRs (three pending confirmation) were seen in patients receiving triplet therapy. A DCR of 100% was observed with doublet therapy and a DCR of 90% was observed with triplet therapy.

"Many patients with advanced non-small cell lung cancer still experience disease progression following initial treatment, underscoring the need for new therapeutic approaches," said Benjamin Philip Levy, MD, Clinical Director of Medical Oncology, Johns Hopkins Sidney Kimmel Cancer Center, at Sibley Memorial Hospital and Associate Professor of Oncology at Johns Hopkins University School of Medicine. "The initial results from the TROPION-Lung02 trial show encouraging safety and efficacy results when combining datopotamab deruxtecan and pembrolizumab with or without platinum chemotherapy and warrant further study in the first-line metastatic setting."

Combinations with datopotamab deruxtecan demonstrated a tolerable safety profile, which supports further evaluation in ongoing studies. Grade 3 or greater treatment-emergent adverse events (TEAEs) occurred in 40% and 60% of patients in the doublet and triplet cohorts, respectively. The most frequent TEAEs of any grade in the doublet and triplet cohorts respectively were stomatitis (56% and 29%), nausea (41% and 48%), decreased appetite (28% and 38%), fatigue (25% and 36%) and anemia (16% and 36%). There were four interstitial lung disease (ILD) events determined as drug-related by an independent adjudication committee across both cohorts; two were adjudicated as grade 1/2 and two were adjudicated as grade 3. No grade 4 or grade 5 ILD events were adjudicated as drug-related. At the time of the data cut-off, there were three potential ILD events pending adjudication. Three deaths occurred (two within the doublet cohort, one in the triplet cohort), none of which were determined as drug-related. Treatment discontinuations due to adverse events occurred in less than 21% of patients and datopotamab deruxtecan dose discontinuation occurred in 13% of patients.

"These early findings from TROPION-Lung02 are promising and represent the first lung cancer trial to report results combining a TROP2 directed antibody drug conjugate with an immune checkpoint inhibitor with or without platinum chemotherapy in patients with advanced or metastatic non-small cell lung cancer," said Gilles Gallant, BPharm, PhD, FOPQ, Senior Vice President, Global Head, Oncology Development, Oncology R&D, Daiichi Sankyo. "These data support the initiation of the TROPION-Lung08 phase 3 trial to further evaluate datopotamab deruxtecan in combination with pembrolizumab as a first-line combination treatment in patients with advanced non-small cell lung cancer without actionable genomic alterations."

"Building on preliminary findings of datopotamab deruxtecan combination therapy in triple negative breast cancer shared earlier this year, these initial results from TROPION-Lung02 reflect the broader promise of combining existing treatments with antibody drug conjugates," said Cristian Massacesi, MD, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca. "We look forward to continuing this important research with the goal of providing a new treatment option for patients with advanced non-small cell lung cancer."

Patients in TROPION-Lung02 receiving doublet therapy were previously-treated with one median line of therapy, including platinum chemotherapy (60%) and immunotherapy (30%). In the triplet cohort, patients previously received platinum chemotherapy (35%) and immunotherapy (38%). Datopotamab deruxtecan-based combination as first-line therapy accounted for 33% and 63% of patients in doublet and triplet cohorts, respectively. As of the May 2, 2022 data cut-off, 53% and 77% of patients remained on the doublet and triplet therapy, respectively.

Summary of TROPION-Lung02 Results
About TROPION-Lung02
TROPION-Lung02 is an ongoing global, open-label, six-cohort phase 1b trial evaluating the safety and efficacy of datopotamab deruxtecan at two dose levels (4 mg/kg and 6 mg/kg) in combination with pembrolizumab (200 mg) with or without four cycles of platinum chemotherapy (carboplatin or cisplatin) in both previously untreated and pretreated patients with advanced or metastatic NSCLC without actionable genomic alterations (e.g., EGFR, ALK, ROS1, NTRK, BRAF, RET, MET or other known actionable alterations).

The primary endpoints of TROPION-Lung02 are dose-limiting toxicities (DLTs) and TEAEs. Secondary endpoints include ORR, duration of response, progression-free survival, overall survival, pharmacokinetics and anti-drug antibodies for datopotamab deruxtecan and pembrolizumab.

TROPION-Lung02 is one of two clinical trial collaborations with Merck & Co., Inc., Rahway, NJ., USA (known as MSD outside of the United States and Canada) evaluating datopotamab deruxtecan in combination with pembrolizumab with or without platinum chemotherapy. The second clinical trial collaboration for the TROPION-Lung08 phase 3 trial is currently enrolling previously untreated patients with PD-L1 high (tumor proportion score ≥ 50%) advanced or metastatic non-small cell lung cancer (NSCLC) without actionable genomic alterations to evaluate the safety and efficacy of datopotamab deruxtecan in combination with pembrolizumab compared to pembrolizumab alone.

About Non-Small Cell Lung Cancer Without Actionable Genomic Alterations
Lung cancer is the second most common cancer and the leading cause of cancer-related mortality worldwide.6 NSCLC is diagnosed at an advanced stage in nearly 50% of patients and often has a poor prognosis with worsening outcomes after each line of subsequent therapy.1,2,3

While the introduction of targeted therapies and checkpoint inhibitors in recent years have improved outcomes for patients with advanced NSCLC, the majority of tumors do not have known actionable genomic alterations.7,8,9,10 Current standard of care in the first-line treatment of patients with advanced NSCLC without actionable genomic alterations is immunotherapy with or without platinum-based chemotherapy, based upon PD-L1 expression. While these therapies may improve survival, at least 40 to 60% of tumors do not respond to initial treatment and disease progression occurs, underscoring the need for new therapeutic approaches and options.11,12,13,14

About TROP2 in Non-Small Cell Lung Cancer
TROP2 (trophoblast cell-surface antigen 2) is a transmembrane glycoprotein that is widely expressed in several types of solid tumors, including NSCLC.15,16,17,18 TROP2 is expressed across all lung cancer subtypes, with the highest expression seen in the majority of adenocarcinoma and squamous cell carcinoma (the most common forms of NSCLC).17,19 No TROP2 directed therapies are currently approved for the treatment of patients with NSCLC.14,20,21

About Datopotamab Deruxtecan (Dato-DXd)
Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, datopotamab deruxtecan is one of three leading ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca’s ADC scientific platform. Datopotamab deruxtecan is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads, an exatecan derivative, via tetrapeptide-based cleavable linkers.

A comprehensive development program called TROPION is underway globally with trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple solid tumors, including triple negative breast cancer, HR positive/HER2 negative breast cancer, NSCLC, small cell lung cancer, urothelial, gastric and esophageal cancer. Trials in combination with other anticancer treatments, such as immunotherapy, also are underway.

About the Daiichi Sankyo and AstraZeneca Collaboration
Daiichi Sankyo Company, Limited (referred to as Daiichi Sankyo) and AstraZeneca entered into a global collaboration to jointly develop and commercialize datopotamab deruxtecan in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for the manufacturing and supply of datopotamab deruxtecan.

On August 9, 2022 Kintara Therapeutics, Inc. (Nasdaq: KTRA) ("Kintara" or the "Company"), a biopharmaceutical company focused on the development of new solid tumor cancer therapies, reported that it has received a Study May Proceed letter from the United States Food and Drug Administration (FDA) to begin its 15 patient study evaluating REM-001 Photodynamic Therapy (PDT) for the treatment of Cutaneous Metastatic Breast Cancer (CMBC) (Press release, Kintara Therapeutics, AUG 9, 2022, View Source [SID1234617898]). This study is intended to aid in the design of a planned phase 3 registrational study.

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"The FDA’s reactivation of our Investigational New Drug application for REM-001 is an important milestone for Kintara," stated Robert E. Hoffman, President and CEO of Kintara. "This clinical study is part of a broad strategy designed to demonstrate proof of concept for our Photodynamic Therapy platform in CMBC, an area of unmet medical need, as well as across other cutaneous metastatic cancers."

PDT is a treatment that uses light sensitive compounds, or photosensitizers, that, when exposed to specific wavelengths of light, act as a catalyst to produce a form of oxygen that induces local tumor cell death. The planned clinical study is expected to enroll 15 patients with CMBC that is refractory or not eligible for radiotherapy or surgery. The study will evaluate cutaneous tumor response using standardized and calibrated 3D digital photography.

"We’re excited to further explore the potential benefits of this second-generation photosensitizer, particularly given the unmet need of CMBC," added Dr. Mario E. Lacouture, Professor and Director of the Oncodermatology Program in the Dermatology Service Department of Medicine at Memorial Sloan Kettering Cancer Center and Chairman of Kintara’s REM-001 Scientific Advisory Board.

On August 9, 2022 Fusion Pharmaceuticals Inc. (Nasdaq: FUSN), a clinical-stage oncology company focused on developing next-generation radiopharmaceuticals as precision medicines, reported financial results for the second quarter ended June 30, 2022 and provided an update on clinical and corporate developments (Press release, Fusion Pharmaceuticals, AUG 9, 2022, View Source [SID1234617877]).

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Chief Executive Officer John Valliant, Ph.D. commented, "We are pleased with the recent FDA clearance of our FPI-2059 investigational new drug (IND) application and the initiation of the Phase 1 clinical study demonstrating our ability to progress into the clinic targeted alpha therapies based on various targeting molecules. The FPI-2059 small molecule targeting NTSR1 has the potential to address several solid tumor indications, including neuroendocrine differentiated prostate, colorectal and pancreatic cancers, for which there is substantial unmet clinical need. Further, we are encouraged by the imaging data we presented at the SNMMI 2022 Annual Meeting that showed pre-administration of cold antibody with FPI-1434 increased tumor binding with a good safety profile."

Dr. Valliant continued, "With three clinical programs and our multi-program partnership with AstraZeneca, we are committed to building a fully integrated radiopharmaceutical organization, marked most recently by our actinium-225 collaboration and supply agreement with Niowave. The agreement provides access to a pre-determined percentage of Niowave’s capacity, access to any excess supply, and the option to invest in future production facilities. This agreement, together with our collaborations with TRIUMF and the Department of Energy, extend our leadership position in actinium supply and meet the needs of our growing pipeline."

Portfolio Update

FPI-1434

In the Phase 1 study, Fusion is exploring various dose levels of FPI-1434 as well as two dosing regimens: one with FPI-1434 alone, and another in which a small dose of cold antibody (naked IGF-1R antibody without the isotope) is administered prior to each dose of FPI-1434. The Company anticipates reporting Phase 1 safety, pharmacokinetics, and imaging data, including any evidence of anti-tumor activity, and details on the dosing regimen, in the first half of 2023. Fusion continues to anticipate the initiation of a Phase 1 combination study with FPI-1434 and KEYTRUDA (pembrolizumab) to occur six to nine months following determination of the recommended Phase 2 dose of FPI-1434 monotherapy.

FPI-1966

The Phase 1, non-randomized, open-label clinical trial of FPI-1966 in patients with solid tumors expressing FGFR3, intended to investigate safety, tolerability and pharmacokinetics and to establish the recommended Phase 2 dose, has been initiated. Fusion expects to dose the first patient in the second half of 2022 and plans to provide updated guidance for preliminary pharmacokinetic, imaging and safety data from the first patient cohort following initial experience with patient screening in order to better predict the cadence of patient enrollment.

FPI-2059

FPI-2059 is a small molecule radioconjugate in development as a targeted alpha therapy for various solid tumors, including neuroendocrine differentiated (NED) prostate, colorectal, and pancreatic cancers. The molecule targets neurotensin receptor 1 (NTSR1), a promising target for cancer treatment, which is overexpressed in several solid tumors. FPI-2059 is based upon Ipsen’s IPN-1087 (previously studied in a Phase 1 clinical trial as a beta-emitting radiopharmaceutical), which Fusion acquired in 2021, and converted to an alpha-emitting radiopharmaceutical using actinium-225.

The U.S. Food and Drug Administration (FDA) cleared Fusion’s IND application for FPI-2059 in June 2022 and study initiation activities are ongoing in a Phase 1, non-randomized, open-label clinical trial in patients with solid tumors expressing NTSR1, intended to investigate safety, tolerability and pharmacokinetics and to establish the recommended Phase 2 dose. Fusion plans to provide guidance on timelines for the FPI-2059 program following site activations and initial experience with patient screening and patient enrollment.

Recent Updates

In June, Fusion presented imaging data from the cold antibody sub-study in the Phase 1 study of FPI-1434 at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) 2022 Annual Meeting. Imaging data from the study demonstrate a favorable gain in [111In]-FPI-1547, the investigational imaging agent, tumor lesion uptake versus normal tissue when FPI-1175, the naked antibody without the isotope, was pre-administered and compared to dosing with FPI-1547 alone. Importantly, sites of improved tumor lesion uptake were independent of anatomic location of disease and included bone, lung, liver, and lymph nodes. Administration of FPI-1547 with and without pre-administration of FPI-1175 was safe without any drug-related Serious Adverse Events or Dose Limiting Toxicities.
In June, Fusion and Niowave, Inc. announced an agreement for the development, production, and supply of actinium-225. Fusion will invest up to $5 million in Niowave to further develop their technology to increase current production capacity of actinium-225, and in return Fusion will have guaranteed access to a pre-determined percentage of Niowave’s capacity of the resulting actinium-225, as well as preferred access to any excess supply produced. As part of the agreement, Fusion will also have an option to invest in future production of actinium-225 to scale with Fusion’s needs.
Second Quarter 2022 Financial Results

Cash and Investments: As of June 30, 2022, Fusion held cash, cash equivalents and investments of $198.4 million, compared to cash, cash equivalents and investments of $220.8 million as of December 31, 2021. Fusion expects its existing cash, cash equivalents and investments as of June 30, 2022, will be sufficient to fund operations into the first quarter of 2024.
Collaboration Revenue: For the second quarter of 2022, Fusion recorded $0.6 million of revenue under the AstraZeneca collaboration agreement.
R&D Expenses: Research and development expenses for the second quarter of 2022 were $12.1 million, compared to $21.1 million for the same period in 2021. The decrease was primarily due to a decrease in platform development and unallocated research and development costs driven by discrete items that occurred during the second quarter of 2021, including common share issuances pursuant to our asset purchase agreements with Ipsen and Rainier Therapeutics, and payments made under our agreement with CPDC for services relating to the validation of Fusion’s manufacturing facility currently under construction which resulted in the recognition of research and development expense during that quarter.
G&A Expenses: General and administrative expenses for the second quarter of 2022 were $7.8 million, compared to $6.6 million for the same period in 2021. The increase was primarily due to an increase in personnel-related costs, corporate costs and professional fees.
Net Loss: For the second quarter of 2022, Fusion reported a net loss of $19.1 million, or $0.44 per share, compared with a net loss of $26.9 million, or $0.63 per share, for the same period in 2021.
Impact of COVID-19

Fusion is experiencing material delays in patient recruitment, enrollment and study site initiations as a result of continued resourcing issues related to COVID-19 at trial sites.

There also remains uncertainty relating to the trajectory of the pandemic, hospital staffing and resource issues, and whether they may cause further delays in patient study recruitment. The impact of related responses and disruptions caused by the COVID-19 pandemic may result in further difficulties or delays in initiating, enrolling, conducting or completing the planned and ongoing trials and the incurrence of unforeseen costs as a result of disruptions in clinical supply or preclinical study or clinical trial delays. The continued impact of COVID-19 on results will largely depend on future developments, which are highly uncertain and cannot be predicted with confidence.