On May 10, 2021 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 first quarter ended March 31, 2021 and provided a corporate update (Press release, Intra-Cellular Therapies, MAY 10, 2021, View Source [SID1234579594]).

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"The acceptance of our sNDAs by the FDA is an important step towards a potential new treatment option for patients living with bipolar depression, a condition with a limited number of approved treatments. While preparing for this significant opportunity, our team will continue to execute on our commercial objectives for CAPLYTA and advance our robust pipeline," said Dr. Sharon Mates, Chairman and CEO of Intra-Cellular Therapies.

First Quarter Financial Highlights:

Total revenues were $15.9 million for the first quarter of 2021, compared to $1.1 million of total revenues for the first quarter of 2020. Net product revenues of CAPLYTA were $15.6 million for the first quarter of 2021, compared to $0.9 million in net product revenues of CAPLYTA for the same period in 2020.
Cost of product sales were $1.5 million in the first quarter of 2021 compared to $0.1 million for the first quarter of 2020.
Research and development (R&D) expenses for the first quarter of 2021 were $15.1 million, compared to $16.0 million for the first quarter of 2020. This decrease is due primarily to a decrease in manufacturing expense and is partially offset by an increase of lumateperone clinical and non-clinical expenses.
Selling, general and administrative (SG&A) expenses were $52.6 million for the first quarter of 2021, compared to $34.1 million for the same period in 2020. This increase is primarily due to an increase in sales related labor costs and commercialization costs.
Net loss for the quarter ended March 31, 2021 was $52.7 million compared to a net loss of $47.4 million for the quarter ended March 31, 2020.
Cash, cash equivalents, restricted cash and investment securities totaled $613.4 million at March 31, 2021, compared to $658.8 million at December 31, 2020.
COMMERCIAL HIGHLIGHTS

Despite the continued impact of COVID-19 on the healthcare system during the first quarter, our commercial organization continued to effectively engage with our prescribing audience through a hybrid model of in-person and virtual interactions, enhanced by digital marketing initiatives.
First quarter CAPLYTA results reflect strong commercial execution delivering continued prescription growth, increasing total prescriptions 23% versus the fourth quarter.
CAPLYTA market access coverage is strong with greater than 95% of covered lives in both Medicare Part D and State Medicaid, the major payer channels in schizophrenia. Our LytaLink program continues to be highly competitive and effective in supporting prescribing physicians and eligible patients’ access to CAPLYTA.
CLINICAL HIGHLIGHTS

Lumateperone – Bipolar Depression Program:

The U.S. Food and Drug Administration (FDA) has accepted for review the sNDAs for lumateperone for the treatment of depressive episodes associated with bipolar I or II disorder (bipolar depression) as monotherapy and as adjunctive therapy with lithium or valproate. The FDA has assigned a PDUFA target action date of December 17, 2021 for these applications.
At the American Psychiatric Association (APA) Annual Meeting held from May 1-3, 2021, we had several presentations describing lumateperone study results. These included results from Study ‘402, a global Phase 3 clinical trial evaluating lumateperone as adjunctive therapy to lithium or valproate in the treatment of major depressive episodes associated with bipolar I or bipolar II disorder and analyses from Study ‘404 highlighting the efficacy results of patients with bipolar depression who exhibit mixed features. Another presentation summarized the overall safety and tolerability profile of the bipolar depression monotherapy program.
Other Lumateperone Programs

Mixed Features program: Study ‘403 evaluating lumateperone 42 mg in patients with major depressive disorder (MDD) and in patients with bipolar depression who exhibit mixed features is ongoing.
Adjunctive MDD program: Clinical conduct in two studies, Studies ‘501 and ‘502, our Phase 3 clinical trials evaluating lumateperone 42 mg as an adjunctive therapy to antidepressants for the treatment of MDD is anticipated to begin later this year.
Lumateperone Long Acting Injectable (LLAI) formulation: Study ITI-007-025, a Phase 1 single ascending dose study of LLAI, a formulation designed to be administered subcutaneously and to maintain therapeutic levels of lumateperone for at least one month is ongoing. Initial results from this study are anticipated in the second half of 2021.
CAPLYTA- Schizophrenia

Announced the publication of "Safety and tolerability of lumateperone 42 mg: An open-label antipsychotic switch study in outpatients with stable schizophrenia" (Correll et al. 2021) in the journal, Schizophrenia Research.
At APA we presented analyses from Study 303, our long-term safety schizophrenia study, evaluating the antidepressant effects of CAPLYTA in patients with schizophrenia with co-morbid depression, with and without concomitant antidepressant treatments.
Other Programs

ITI-1284 program: We introduced ITI-1284 ODT-SL, a deuterated form of lumateperone, a new molecular entity formulated as an orally disintegrating tablet for sublingual administration. We plan to initiate studies evaluating ITI-1284 ODT-SL for the treatment of behavioral disturbances in patients with dementia, the treatment of dementia-related psychosis and the treatment of certain depressive disorders in the elderly.
Phosphodiesterase type I inhibitor (PDE1) program: Our PDE1 inhibitor program is focused on diseases in which the PDE1 enzyme is over-expressed and/or abnormal immune cell function contributes to disease pathology. This suggests therapeutic potential across a variety of diseases, including neurological and cardiovascular diseases, as well as cancer.
We plan to advance our lead molecule, lenrispodun (ITI-214), into a Phase 2 clinical study in Parkinson’s disease in the second half of 2021.
At the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting, we presented preclinical data supporting the potential of PDE1 inhibition to enhance the anti-tumor effects of immunotherapies by altering the tumor micro-environment. Our prior studies elucidating the neuroprotective and anti-inflammatory effects of PDE1 inhibitors in the brain by regulating microglia function (brain resident macrophage-like cells) led to our exploration of similar effects outside the brain. Therefore, we hypothesized PDE1 inhibition could result in antitumor effects by controlling similar functions of macrophages in the tumor micro-environment. Our experiments indicate PDE1 inhibition prevents the migration and accumulation of monocytes and macrophages in the tumor micro-environment and could represent a novel and broadly applicable approach to the treatment of immune responsive cancers.

ITI-333 program in opioid use disorder: Study ITI-333-001, a Phase 1 single ascending dose study evaluating the safety, tolerability and pharmacokinetics of ITI-333 in healthy volunteers is ongoing. Results from this study are anticipated in the second half of 2021.
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-(844) 835-6563 (U.S.) or 1-(970) 315-3916 (international) to listen to the live conference call. The conference ID number for the live call is 3244409. Please dial in approximately 10 minutes prior to the call.

CAPLYTA (lumateperone) is indicated for the treatment of schizophrenia in adults. CAPLYTA is available in 42 mg capsules.

Important Safety Information

Boxed Warning: 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.

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.
Sleepiness and Trouble Concentrating. 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, moderate or strong CYP3A4 inhibitors and UGT 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. Use of CAPLYTA should be avoided in patients with moderate or severe liver problems.

Adverse Reactions: The most common adverse reactions in clinical trials with CAPLYTA vs. placebo were somnolence/sedation (24% vs. 10%) and dry mouth (6% vs. 2%).

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

About CAPLYTA (lumateperone)

CAPLYTA 42mg/day is an oral, once daily atypical antipsychotic approved for the treatment of schizophrenia of adults. While the mechanism of action of CAPLYTA in the treatment of schizophrenia 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 investigated for the treatment of bipolar depression, depression and other neuropsychiatric and neurological disorders. CAPLYTA is not FDA approved for these disorders.

On May 10, 2021 TG Therapeutics, Inc. (NASDAQ: TGTX) reported its financial results for the first quarter ending March 31, 2021 and recent company developments, along with a business outlook for 2021 (Press release, TG Therapeutics, MAY 10, 2021, View Source [SID1234579593]).

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Michael S. Weiss, the Company’s Executive Chairman and Chief Executive Officer, stated, "2021 has been an incredibly impactful year, kicking off with our first approval coming ahead of schedule for UKONIQ to treat both relapsed or refractory Marginal Zone Lymphoma and Follicular Lymphoma. That was followed by the completion of a BLA submission for ublituximab in combination with UKONIQ (U2) to treat patients with CLL, and the full presentation of positive results from the ULTIMATE I & II Phase 3 trials in relapsing forms of MS. As a fully integrated commercial organization we are pleased with our progress thus far with the UKONIQ launch and we look forward to continuing to build our commercial infrastructure to support the potential approval and commercialization of U2 in CLL and ublituximab in RMS."

2021 Highlights & Recent Developments

UKONIQTM (umbralisib) in Relapsed or Refractory Marginal Zone Lymphoma & Follicular Lymphoma

Received accelerated approval from the U.S. Food and Drug Administration (FDA) on February 5, 2021 for UKONIQ to treat adult patients with relapsed or refractory marginal zone lymphoma (MZL) who have received at least one prior anti-CD20 based regimen and adult patients with relapsed or refractory follicular lymphoma (FL) who have received at least three prior lines of systemic therapy.
Launch efforts underway across the U.S. UKONIQ has payor coverage for 85-90% of Medicare and commercial lives and is included in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for MZL and FL, consistent with the FDA-approved indications.
Published results from the UKONIQ monotherapy cohorts of the UNITY-NHL Phase 2b trial in patients with relapsed or refractory indolent non-Hodgkin Lymphoma (NHL) in the Journal of Clinical Oncology.
Ublituximab plus UKONIQ (U2) in Chronic Lymphocytic Leukemia

Completed a rolling submission of a Biologics License Application (BLA) to the FDA requesting approval of U2, as a treatment for patients with chronic lymphocytic leukemia (CLL), including both previously untreated and relapsed/refractory patients, based on the positive results from the UNITY-CLL Phase 3 trial.
Completed enrollment in the ULTRA-V Phase 2 trial, and launched the ULTRA-V Phase 3 randomized trial evaluating the triple combination of U2 plus venetoclax in patients with treatment naïve and relapsed or refractory CLL.
Ublituximab in Multiple Sclerosis

Presented positive results from the ULTIMATE I & II Phase 3 trials at the American Academy of Neurology 2021 Annual Meeting. Both trials met their primary endpoint with ublituximab treatment demonstrating a statistically significant reduction in annualized relapse rate (ARR) over a 96-week period compared to teriflunomide in patients with relapsing forms of multiple sclerosis (RMS).
TG-1701 in B-cell Malignancies

Updated data from TG-1701, our BTK inhibitor, as a monotherapy and in combination with U2 in patients with B-cell malignancies has been accepted for presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting being held in June 2021.
Remaining Key Objectives for 2021

Focus on the commercialization of UKONIQ in relapsed/refractory MZL and FL and expand commercialization capabilities in preparation for a potential launch of U2 for CLL and ublituximab in MS
Submit a BLA for ublituximab for the treatment of patients with RMS in Q3 2021, based on positive results from the ULTIMATE I & II Phase 3 trials
Receive notification from the FDA that the BLA for U2 in CLL has been accepted for filing and work closely with the Agency on its review of the application
Enroll into the newly launched ULTRA-V Phase 3 trial evaluating the triple combination of U2 plus venetoclax
Continue to advance our early pipeline candidates including TG-1501 (cosibelimab), TG-1701 and TG-1801
Financial Results for the Three Months Ended March 31, 2021

Product Revenue, net: Product revenue, net was approximately $0.8 million for the three months ended March 31, 2021, compared to zero during the comparable period in 2020. Net product revenues represent U.S. sales from our sole commercial product, UKONIQ, which received accelerated approval from the FDA on February 5, 2021, with launch later in the month.

R&D Expenses: Total research and development (R&D) expense was $63.1 million for the three months ended March 31, 2021, compared to $36.0 million for the three months ended March 31, 2020. The increase was due primarily to licensing milestone fees of approximately $14.0 million incurred during the first quarter of 2021 and an increase of approximately $5.5 million in non-cash compensation R&D expenses over the comparable quarter in 2020.

SG&A Expenses: Total selling, general and administrative (SG&A) expense was $26.8 million for the three months ended March 31, 2021 and $14.3 million for the three months ended March 31, 2020. The increase was due primarily to increased personnel and other selling, general and administrative costs associated with preparations for, and now execution of, the commercial launch of UKONIQ. We expect our selling, general and administrative expenses to increase for the remainder of 2021 in preparation for the potential launch of ublituximab as part of the U2 combination for CLL and as a monotherapy in MS.

Net Loss: Net loss was $90.6 million for the three months ended March 31, 2021 compared to $51.1 million for the three months ended March 31, 2020. Excluding non-cash compensation, the net loss for the three months ended March 31, 2021 was approximately $74.0 million, compared to a net loss of $40.0 million for the three months ended March 31, 2020.

Cash Position and Financial Guidance: Cash, cash equivalents and investment securities were $523.8 million as of March 31, 2021, which the Company believes will be sufficient to fund the Company’s planned operations into 2023.
CONFERENCE CALL INFORMATION
The Company will host a conference call today, May 10, 2021, at 8:30 AM ET, to discuss the Company’s first quarter ended March 31, 2021 financial results and provide a business outlook for the remainder of 2021.

To participate in the conference call, please call 1-877-407-8029 (U.S.), 1-201-689-8029 (outside the U.S.), Conference Title: TG Therapeutics. A live audio webcast will be available on the Events page, located within the Investors & Media section, of the Company’s website at View Source An audio recording of the conference call will also be available for a period of 30 days after the call.

On May 10, 2021 ImmunoGen Inc. (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, reported financial results for the quarter ended March 31, 2021 (Press release, ImmunoGen, MAY 10, 2021, View Source [SID1234579591]).

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"During the first quarter, we advanced our portfolio of innovative ADCs and accelerated preparations for two potential product launches next year," said Mark Enyedy, ImmunoGen’s President and Chief Executive Officer. "We saw a limited delay in patient enrollment in the pivotal SORAYA trial for our lead program, mirvetuximab soravtansine, which has shifted the anticipated timing of top-line data from the third into the fourth quarter of this year and the projected submission of the BLA into the first quarter of 2022. We have also experienced some COVID-related impact on accrual to our confirmatory MIRASOL trial and now expect the read-out on the primary endpoint to move from the second into the third quarter of 2022. Beyond SORAYA and MIRASOL, we are commencing several studies to move mirvetuximab into earlier lines of ovarian cancer therapy, including an investigator-sponsored trial of mirvetuximab in combination with carboplatin in the neoadjuvant setting that initiated this quarter. We are also supporting a randomized study comparing mirvetuximab combined with carboplatin to standard of care in patients with recurrent platinum-sensitive disease and have submitted a protocol to FDA for a single-arm study of mirvetuximab monotherapy in later-line platinum-sensitive patients, with both studies anticipated to begin enrollment in the second half of this year. Finally, we were pleased to receive notice that mature data from our mirvetuximab plus Avastin doublet cohort in recurrent ovarian cancer, regardless of platinum status, have been selected for an oral presentation at ASCO (Free ASCO Whitepaper) in June."

Enyedy added, "We continued enrollment for our second pivotal program, IMGN632, in patients with frontline and relapsed/refractory BPDCN, with top-line data expected in the first half of 2022. IMGN632 is also in ongoing development in AML, both as a monotherapy and in combinations. Moving to our earlier-stage portfolio, we presented preclinical data at AACR (Free AACR Whitepaper) last month on IMGC936, our first-in-class ADAM9-targeting ADC, demonstrating anti-tumor activity in multiple solid tumor models, and we advanced dose escalation in the Phase 1 study for this program. IND-enabling activities for our next-generation anti-FRα ADC, IMGN151, are on track to submit an application to the FDA by the end of 2021. With pre-commercial activities underway, we look forward to a meaningful year ahead with a number of important milestones across the business as we work towards bringing our first two therapies to market next year."

RECENT PROGRESS

Further enrolled patients in the pivotal SORAYA and confirmatory MIRASOL trials.
Supported initiation of an investigator-sponsored trial of mirvetuximab plus carboplatin in the neoadjuvant setting.
Submitted to the US Food and Drug Administration (FDA) a single-arm study protocol for mirvetuximab monotherapy in later-line platinum-sensitive ovarian cancer patients.
Advanced accrual of the pivotal 801 Phase 1/2 study of IMGN632 in frontline and relapsed/refractory (R/R) blastic plasmacytoid dendritic cell neoplasm (BPDCN) patients.
Continued patient enrollment in the 802 Phase 1b/2 study of IMGN632 in combination with Vidaza (azacitidine) and Venclexta (venetoclax) in R/R and frontline acute myeloid leukemia (AML) patients and as a monotherapy in minimal residual disease positive (MRD+) AML.
Presented preclinical data on IMGC936, our novel ADAM9-targeting ADC in co-development with MacroGenics, in a poster at the virtual American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting.
Moved through dose-escalation cohorts in the Phase 1 study of IMGC936 in multiple solid tumor types.
Progressed activities to support an investigational new drug (IND) application for IMGN151.
ANTICIPATED UPCOMING EVENTS

Generate top-line pivotal SORAYA data in the fourth quarter of 2021 and submit the biologics license application (BLA) in the first quarter of 2022 to support potential accelerated approval in 2022.
Complete patient enrollment in MIRASOL and generate top-line data in the third quarter of 2022.
Present mature data from the Phase 1b FORWARD II cohort evaluating mirvetuximab in combination with Avastin (bevacizumab) in recurrent ovarian cancer in an oral presentation at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in June.
Initiate a single-arm study of mirvetuximab monotherapy in recurrent platinum-sensitive ovarian cancer in the second half of 2021 to support potential label expansion.
Support the start of a randomized Phase 2 investigator-sponsored study of mirvetuximab plus carboplatin in recurrent platinum-sensitive ovarian cancer in the second half of 2021.
Present initial AML combination data for IMGN632 at the 2021 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December.
Complete dose escalation in the Phase 1 study evaluating IMGC936, with initial data anticipated in early 2022.
Submit the IND application for IMGN151 by the end of 2021.
FINANCIAL RESULTS

Revenues for the quarter ended March 31, 2021 were $15.7 million, compared with $13.3 million for the quarter ended March 31, 2020, which consisted primarily of non-cash royalty revenues.

Operating expenses for the first quarter of 2021 were $44.6 million, compared with $37.1 million for the same quarter in 2020. The increase was largely driven by research and development expenses, which were $34.4 million in the first quarter of 2021, compared with $27.4 million for the first quarter of 2020. This increase was primarily due to greater clinical trial expenses driven by costs related to the MIRASOL, SORAYA, and IMGC936 studies, greater external manufacturing costs, and greater personnel and temporary staffing costs. General and administrative expenses for the first quarter of 2021 increased to $10.2 million, compared to $8.9 million for the first quarter of 2020, primarily due to increased professional fees and personnel costs, including greater stock-based compensation. Operating expenses for the first quarter of 2020 included a $0.8 million restructuring charge related to retention costs.

Net loss for the first quarter of 2021 was $34.1 million, or $0.17 per basic and diluted share, compared to a net loss of $29.1 million, or $0.17 per basic and diluted share, for the first quarter of 2020. Weighted average shares outstanding increased to 198.8 million for the 2021 period from 166.9 million in the prior year.

ImmunoGen had $283.1 million in cash and cash equivalents as of March 31, 2021, compared with $293.9 million as of December 31, 2020, and had $2.1 million of convertible debt outstanding in each period. Cash used in operations was $44.6 million for the first three months of 2021, compared with cash used in operations of $28.3 million for the same period in 2020. Capital expenditures were $(0.9) million for the first quarter of 2021, compared with net proceeds from the sale of equipment of $1.4 million for the first quarter of 2020.

FINANCIAL GUIDANCE

ImmunoGen’s financial guidance for 2021 remains unchanged:

revenues between $65 million and $75 million;
operating expenses between $200 million and $210 million; and
cash and cash equivalents at December 31, 2021 to be between $140 million and $150 million.
ImmunoGen expects that its current cash will fund operations into the second half of 2022.

CONFERENCE CALL INFORMATION

ImmunoGen will hold a conference call today at 8:00 a.m. ET to discuss these results. To access the live call by phone, dial (877) 621-5803; the conference ID is 9982696. The call may also be accessed through the Investors and Media section of immunogen.com. Following the call, a replay will be available at the same location.

On May 10, 2021 Sonnet BioTherapeutics Holdings, Inc., (NASDAQ:SONN) a biopharmaceutical company developing innovative targeted biologic drugs, reported that it has completed a successful preclinical nonhuman primate (NHP) GLP repeat-dose study of SON-1010, a proprietary version of Interleukin 12 (IL-12) configured using Sonnet’s Fully Human Albumin Binding (FHAB) platform (Press release, Sonnet BioTherapeutics, MAY 10, 2021, View Source [SID1234579590]). The FHAB technology targets tumor and lymphatic tissue, providing a mechanism for dose sparing and an opportunity to improve the safety and efficacy profile of not only IL-12, but a variety of potent immunomodulators.

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The objectives of the study were to evaluate the toxicity of SON-1010 in NHP using a subcutaneous, repeat-dose regimen at three different dose levels versus untreated controls and to evaluate the potential reversibility of any adverse findings.

Pankaj Mohan, Ph.D., Sonnet founder and CEO, commented, "This GLP study was an important milestone to support an IND with the FDA. SON-1010 has now accrued, along with previous non-GLP data, a significant NHP toxicology dataset. The NHP data continues to demonstrate that SON-1010 appears to be safe and is eliciting the expected immune responses that we believe could position this as an effective treatment for multiple types of cancer."

Study results included:

The No Observed Adverse Event Level (NOAEL) following repeated administration was more than 50 times the anticipated equivalent human clinical dose in NHP with no evidence of cytokine release syndrome.
Pharmacokinetic (PK) analysis of serum samples confirmed an enhanced profile of IL12-FHAB over recombinant human IL-12, with a half-life around 40 hours in NHP.
A significant increase in Interferon-γ, a key pleiotropic cytokine associated with anti-tumor mechanisms, was observed following dosing with IL12-FHAB.
SON-1010 related changes in clinical observations, body weight, clinical pathology, cytokines, and immunophenotyping were seen, all of which were consistent with on-target effects previously observed in nonhuman primates.
By Day 38 all study subjects recovered to baseline (pre-study) values.
Repeat dosing administration was tolerated at all dose levels examined.
Richard T. Kenney, M.D., Chief Medical Officer, commented, "Interleukin-12 is a key immunomodulator that bridges innate and adaptive immunity, but showed toxicity in the first human trials over two decades ago. Careful subcutaneous administration of IL-12 has been shown to be a safe dosing approach, even in healthy volunteers. Given that IL12-FHAB has an extended half-life, tolerable doses can be given at longer dosing intervals. SON-1010 has IL-12 attached to a proprietary fully human albumin binding construct, which provides the longer half-life and targeting capability that may be needed to treat tumors. The NHP data suggests that our candidate will be well tolerated. We believe that this novel approach can lead to an effective treatment regimen for multiple types of cancer".

Sonnet’s cell-based manufacturing platform coupled with an intensified perfusion process using state-of-the-art technologies allows rapid scale-up for future commercial manufacturing. Our mammalian cell culture system enables glycosylation, thereby reducing the risk of inducing immunogenicity with IL12-FHAB. We are on track for providing GMP material for initiation of the clinical trial in 2H 2021.

On May 10, 2021 IDEAYA Biosciences, Inc. (Nasdaq:IDYA), a synthetic lethality focused precision medicine oncology company committed to the discovery and development of targeted therapeutics, reported financial results for the first quarter ended March 31, 2021 (Press release, Ideaya Biosciences, MAY 10, 2021, View Source [SID1234579589]).

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"We are excited to advance IDE397, a potential best-in-class MAT2A inhibitor, in the Phase 1 dose escalation for evaluation in patients with MTAP deletion tumors, including in non-small cell lung cancer (NSCLC). We are also continuing to invest in our preclinical synthetic lethality programs, including our PARG and Pol Theta programs for patients with HRD tumors, where we are targeting a development candidate for both programs in 2021," said Yujiro S. Hata, Chief Executive Officer and President of IDEAYA Biosciences.

"We are excited by the preliminary darovasertib monotherapy overall survival data in MUM and look forward to receiving FDA regulatory guidance based on the data in the second half of 2021. We are also executing on our darovasertib clinical combination strategy and are encouraged by the early partial responses observed in the combination arms, including now in the crizotinib combination. Importantly, the 54% tumor reduction by RECIST 1.1 observed in a patient treated with the darovasertib and crizotinib combination is the deepest partial response we have seen to date in the darovasertib Phase 1/2 clinical trial," said Matthew Maurer, M.D., Vice President, Head of Clinical Oncology and Medical Affairs, IDEAYA Biosciences.

Program Updates
Key highlights for IDEAYA’s pipeline programs include:
IDE397 (MAT2A)
IDEAYA is evaluating IDE397, a potent and selective small molecule inhibitor targeting methionine adenosyltransferase 2a (MAT2A), in patients having solid tumors with methylthioadenosine phosphorylase (MTAP) deletion, a patient population estimated to represent approximately 15% of solid tumors. IDEAYA is leading early clinical development of IDE397. Subject to exercise of its option, GlaxoSmithKline (GSK) will lead later stage global clinical development. Highlights:

Initiated a Phase 1 clinical trial designated as IDE397-001 (ClinicalTrials.gov Identifier: NCT04794699) to evaluate IDE397 under an investigational new drug application
Completed enrollment into an initial dose escalation cohort of the Phase 1 clinical trial
Clinical development plans for IDE397 include a dose escalation portion of the Phase 1 clinical trial in which IDEAYA is enrolling patients having solid tumors with MTAP gene deletion. Patients are being identified by next generation sequencing (NGS) or by MTAP immunohistochemistry (IHC) assay with confirmatory NGS
Subject to satisfactory completion of the dose escalation portion of the Phase 1 clinical trial, IDEAYA plans to enroll MTAP deletion patients into expansion arms in NSCLC and potentially in other solid tumor indications such as esophageal, gastric, bladder, head and neck, or pancreatic cancers
Planning to obtain patient biopsies from the dose escalation and expansion portions of the clinical trial for translational research, including evaluation of certain pharmacodynamic, or PD, biomarkers, such as peripheral S-adenosyl methionine (SAM), tumor SAM and tumor symmetric dimethylarginine (SDMA)
Program objective is to obtain preliminary clinical PD data from the dose-escalation portion of the IDE397 monotherapy Phase 1 clinical trial in the second half of 2021
Demonstrated preclinical efficacy of monotherapy IDE397 in a study of over forty solid tumor patient derived xenograft (PDX) models with homozygous MTAP deletions across a range of solid tumor types, including NSCLC, esophageal, gastric, bladder, head and neck, and pancreatic cancers; study data was reported at AACR (Free AACR Whitepaper) 2021 and showed:
tumor regressions, with >100% tumor growth inhibition, or TGI, in multiple PDX models across multiple solid tumor types, including in NSCLC as well as in bladder and gastric cancer models
>75% TGI in approximately 50% of models and across major solid tumor types
>60% TGI in approximately 75% of models and across major solid tumor types
dose-dependent modulation of PD biomarkers, including SDMA and SAM
Observed single-agent IDE397 preclinical activity in NSCLC PDX models, demonstrating >60% TGI in 11 independent PDX models out of 13 models evaluated in the MTAP-deletion PDX panel study, including in 7 of 9 NSCLC adenocarcinoma PDX models, and in 4 of 4 NSCLC squamous carcinoma PDX models evaluated, and demonstrating tumor regressions in 2 of 4 NSCLC squamous PDX models, including one complete response
Showed correlation of in vivo efficacy with PD modulation of tumor SDMA and tumor SAM in a study evaluating IDE397 in an MTAP-deletion NSCLC CDX model
Reported preclinical analyses of genomic and metabolic effects of pharmacological inhibition of MAT2A in an isogenic cell pair and of proliferation effects in a panel of MTAP wild type and MTAP-deleted cell lines at AACR (Free AACR Whitepaper) 2021
Observed in vivo efficacy of IDE397 in combination with a taxane, showing enhanced TGI in a pancreatic cancer PDX model, and separately in combination with a PRMT inhibitor, showing enhanced TGI in an HCT116 MTAP-null CDX model
PARG
IDEAYA is advancing preclinical research for an inhibitor of poly (ADP-ribose) glycohydrolase (PARG) in patients having tumors with a defined biomarker based on genetic mutations and/or molecular signature. PARG is a novel target in the same clinically validated biological pathway as poly (ADP-ribose) polymerase (PARP). IDEAYA owns or controls all commercial rights in its PARG program. Highlights:

Identified a novel and proprietary HRD biomarker to guide patient selection, with validation in vitro and in vivo in CDX models across multiple solid tumor indications
Demonstrated PARGi dose-dependent in vivo efficacy as monotherapy with tumor regression or stasis in ovarian, gastric and breast cancer CDX models
Observed in vivo efficacy with enhanced TGI or tumor regressions relative to niraparib, a PARPi, in multiple CDX models, including in a niraparib-resistant CDX model
Showed tumor regressions in multiple breast cancer PDX models with defined genetic and subtyping profiles
Reported preclinical data at AACR (Free AACR Whitepaper) 2021, including pharmacological inhibition of PARG in a panel of homologous recombination deficient cell lines and in CDX and PDX models
Subject to further preclinical studies, IDEAYA is targeting to identify a PARG inhibitor development candidate in 2021
Pol Theta
IDEAYA’s DNA Polymerase Theta, (Pol Theta) program targets tumors with BRCA or other homologous recombination deficiency, or HRD, mutations. IDEAYA and GSK are collaborating on ongoing preclinical research, including small molecules and protein degraders, and GSK will lead clinical development for the Pol Theta program. Highlights:

Demonstrated in vivo efficacy with tumor regression in BRCA2 -/- xenograft model with IDEAYA Pol Theta inhibitor in combination with niraparib, a GSK PARP inhibitor; and
Subject to further preclinical studies, IDEAYA is targeting selection of a Pol Theta inhibitor development candidate in 2021
Werner Helicase
IDEAYA is advancing preclinical research for an inhibitor targeting Werner Helicase for tumors with high microsatellite instability (MSI). IDEAYA and GSK are collaborating on ongoing preclinical research, and GSK will lead clinical development for the Werner Helicase program. Highlights:

observed dose-dependent cellular viability effect and dose-dependent cellular PD response in multiple endogenous MSI high cell lines
Demonstrated in vivo efficacy and PD response in relevant MSI high models
Other Synthetic Lethality Pipeline Programs
IDEAYA is advancing additional preclinical research programs to identify small molecule inhibitors for an MTAP-synthetic lethality target, as well as for multiple distinct DNA Damage Targets for patients with solid tumors characterized by a proprietary biomarker or a gene signature.

Darovasertib (IDE196)
IDEAYA continues to execute on its clinical trial strategy to evaluate darovasertib (IDE196), a potent and selective PKC inhibitor.

IDEAYA is evaluating darovasertib in metastatic uveal melanoma (MUM) as monotherapy and in combination therapies, including combinations of darovasertib / binimetinib and independently, darovasertib / crizotinib. The company is continuing to enroll MUM patients into each of these combination arms of the Phase 1/2 clinical trial, and it targeting to provide a clinical data update for the darovasertib combination(s) in the second half of 2021. Based on preliminary monotherapy clinical data in MUM and its mechanism of action, we anticipate darovasertib clinical activity independent of Human Leukocyte Antigen (HLA) status in GNAQ/11-mutation cancers.

The company is also evaluating darovasertib as monotherapy outside of MUM, with a focus in GNAQ/11-mutation skin melanoma.

Darovasertib Monotherapy
IDEAYA has completed enrollment into its ongoing Phase 1/2 clinical trial evaluating darovasertib as monotherapy in MUM patients. IDEAYA is targeting to receive FDA guidance in H2 2021 on potential regulatory path, based on the preliminary darovasertib monotherapy overall survival data in MUM. The company is continuing enrollment into its ongoing basket trial evaluating darovasertib as monotherapy in patients having non-MUM tumors harboring GNAQ or GNA11 activating mutations. The company’s development strategy in the monotherapy non-MUM GNAQ/11 arm of the clinical trial is focused on skin melanoma. Highlights:

Reported interim clinical data from Phase 1/2 clinical trial arm evaluating monotherapy darovasertib in predominantly second and third line (2L/3L) and heavily pre-treated out to seventh or eighth line (7L/8L) MUM patients. As of data and analyses cutoff on April 13, 2021 based on preliminary data from an unlocked database:
Enrolled an aggregate of 81 darovasertib monotherapy BID MUM patients across the IDEAYA and Novartis Phase 1/2 clinical trials, with 81 patients evaluable for safety and 75 patients evaluable for efficacy pursuant to RECIST 1.1 guidelines
Observed 57% 1-year overall survival (OS) with 95% confidence interval (44%, 69%), in predominantly 2L/3L and heavily pretreated to 7L/8L patients
Observed median OS of 13.2 months with 95% confidence interval (10.7 months, not reached), in predominantly 2L/3L and heavily pretreated to 7L/8L patients
Historical 37% 1-year OS and median OS of ~7 months have been reported in similar 2L/3L+ MUM patient population (Rantala 2019)
Observed tumor reduction in 61% (n=46) of 75 evaluable MUM patients pursuant to RECIST 1.1 guidelines, including 15 patients (20%) with >30% target lesion reduction, and one confirmed complete response
Reported preliminary clinical data from Phase 1/2 clinical basket trial arm evaluating monotherapy darovasertib in skin melanoma patients. As of data and analyses cutoff of April 13, 2021 based on preliminary data from an unlocked database:
Enrolled 7 darovasertib monotherapy BID skin melanoma patients in the IDEAYA Phase 1/2 clinical trial, with 7 patients evaluable for safety and 5 patients evaluable for efficacy pursuant to RECIST 1.1 guidelines
Observed tumor reduction in 80% (n=4) of 5 evaluable skin melanoma patients pursuant to RECIST1.1 guidelines, including one confirmed PR
An aggregate of 88 patients were evaluable for safety across Phase 1/2 arms evaluating darovasertib in MUM and skin melanoma patients. As of the April 13, 2021 data and analyses cutoff, and based on preliminary data from an unlocked database, the overall safety profile of darovasertib monotherapy is consistent with prior experience and includes primarily common low grade but manageable GI and skin toxicities
Preliminary clinical data from darovsertib monotherapy arm shows that darovasertib activity is independent of HLA status
Darovasertib / Binimetinib Combination Therapy
IDEAYA is continuing patient enrollment into the darovasertib / binimetinib combination arm of the Phase 1/2 clinical trial under the clinical trial collaboration and supply agreement with Pfizer. Highlights:

Initiated dose expansion evaluating the darovasertib / binimetinib combination in MUM based on early clinical activity
Amended the clinical trial collaboration and supply agreement with Pfizer to support target enrollment of approximately 40 patients in the darovasertib and binimetinib clinical combination arm
Reported preliminary clinical data from Phase 1/2 clinical trial arm evaluating the darovasertib / binimetinib combination in MUM patients, predominantly as second line, third line (2L / 3L) or later lines of treatment. As of data and analyses cutoff of April 13, 2021 based on preliminary data from an unlocked database:
24 MUM patients have enrolled in the darovasertib and binimetinib combination study and 14 of these patients were evaluable, including eight patients dosed in the Phase 1/2 dose expansion cohort of the combination study
Observed 22% (n=2) partial responses (PR), including one confirmed PR and on unconfirmed PR awaiting a confirmatory scan, of nine evaluable MUM patients with at least two post-baseline scans pursuant to RECIST 1.1 guidelines
Observed tumor reduction in 79% (n=11) of 14 evaluable MUM patients with at least one post-baseline scan pursuant to RECIST1.1 guidelines
Drug-related adverse events observed in the darovasertib and binimetinib combination arm in MUM, as of April 13, 2021 data and analyses cutoff based on preliminary data from an unlocked database, primarily include: serious adverse events of liver toxicity, nausea and vomiting, and syncope; and adverse events that occurred in greater than 10% of patients of nausea, vomiting, diarrhea, rash, edema, aminotransaminase, or AST increase, alanine aminotransferase, or ALT, increase and creatine phosphokinase increase
Darovasertib / Crizotinib Combination Therapy
IDEAYA is continuing patient enrollment into the darovasertib / crizotinib combination arm of the Phase 1/2 clinical trial under the clinical trial collaboration and supply agreement with Pfizer. Highlights:

6 MUM patients have enrolled in the darovasertib and crizotinib combination study and 2 of these patients were evaluable for response with one post-baseline scan
Observed early clinical efficacy of the darovasertib and crizotinib combination in MUM. As of data and analyses cutoff on May 5, 2021 based on preliminary data from an unlocked database, these data showed:
tumor reduction in 2 of 2 evaluable patients in a first cohort
one unconfirmed partial response in a 3rd-line patient, with a 54% tumor reduction, which is the deepest response, as reflected by the largest percentage reduction in tumor size, reported in the darovasertib clinical trial to date; this patient is awaiting a confirmatory scan
Drug-related adverse events observed in the darovasertib and crizotinib combination arm in MUM as of May 5, 2021, based on preliminary data from an unlocked database, primarily include: serious adverse events of syncope and hypotension, each of which resolved with patients continuing dosing; and adverse events that occurred in at least two of the six treated patients of nausea, diarrhea, vomiting, edema, decreased appetite, and syncope.
Initiated dose expansion for a cohort of the Phase 1/2 darovasertib / crizotinib combination arm, with additional dose exploration ongoing
Observed preclinical synergies between darovasertib and crizotinib in relevant cellular models under conditions simulating a tumor microenvironment in the liver, the site of approximately 90% of uveal melanoma metastases, as reported at AACR (Free AACR Whitepaper) 2021
Correlated cMET expression and activation to observed clinical response based on a retrospective analysis of human clinical biopsies from the Novartis darovasertib Phase 1 clinical trial, supporting cMET expression / activation as potential combination agent
General
IDEAYA continues to monitor Covid-19 and its potential impact on clinical trials and timing of clinical data results. Initiation of clinical trial sites, patient enrollment and ongoing monitoring of enrolled patients, including obtaining patient computed tomography (CT) scans, may be impacted for IDEAYA clinical trials evaluating IDE397 and darovasertib; the specific impacts are currently uncertain.

Corporate Updates
IDEAYA’s net losses were $9.0 million and $5.1 million for the three months ended March 31, 2021 and December 31, 2020, respectively. As of March 31, 2021, the company had an accumulated deficit of $136.0 million.

As of March 31, 2021, IDEAYA had cash, cash equivalents and marketable securities of $310.4 million. IDEAYA supplemented its first-quarter-end cash, cash equivalents and marketable securities with an additional $14.6 million in aggregate gross proceeds received subsequent to quarter end from the sale and issuance of common stock at a weighted average sale price of $22.99 per share under an at-the-market offering pursuant to the January 2021 Sales Agreement with Jefferies as sales agent.

IDEAYA believes that its cash, cash equivalents and marketable securities will be sufficient to fund our planned operations into 2024. These funds will support the company’s efforts through potential achievement of multiple preclinical and clinical milestones across multiple programs.

Our updated corporate presentation is available on our website, at our Investor Relations page: View Source

Financial Results
As of March 31, 2021, IDEAYA had cash, cash equivalents and short-term marketable securities totaling $310.4 million. This compared to cash, cash equivalents and short-term and long-term marketable securities of $283.6 million at December 31, 2020. The increase was primarily due to $41.8 million in net proceeds received through March 31, 2021 from issuance of common stock under at-the-market offerings pursuant to the August 2020 Sales Agreement and January 2021 Sales Agreement with Jefferies as sales agent offset by cash used in operations and purchases of property and equipment.

Collaboration revenue for the three months ended March 31, 2021 totaled $7.2 million compared to $10.6M for the three months ended December 31, 2020. Collaboration revenue was recognized for the performance obligations satisfied through March 31, 2021 under the GSK Collaboration Agreement.

Research and development (R&D) expenses for the three months ended March 31, 2021 totaled $11.6 million compared to $12.1 million for the three months ended December 31, 2020. The decrease was primarily due to a decrease in external clinical development expenses for IDE397 and darovasertib and a decrease in fees to CROs, CMOs and external consultants related to our lead product candidates, offset by an increase in R&D headcount costs.

General and administrative (G&A) expenses for the three months ended March 31, 2021 totaled $4.8 million compared to $3.8 million for the three months ended December 31, 2020. The increase was primarily due to an increase in G&A headcount costs, an increase in legal patent expense, and an increase in costs related to the filing of our shelf registration statement on Form S-3 during the quarter.

The net loss for the three months ended March 31, 2021 was $9.0 million compared to $5.1 million for the three months ended December 31, 2020. Total stock compensation expense for the three months ended March 31, 2021 was $1.9 million compared to $1.0 million for the three months ended December 31, 2020.