On November 9, 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 third quarter ended September 30, 2021 and provided a corporate update (Press release, Intra-Cellular Therapies, NOV 9, 2021, View Source [SID1234595183]).

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"We are excited about the progress we have made during the third quarter in the commercialization of CAPLYTA in schizophrenia and in the advancement of our development programs. In addition, our bipolar depression launch preparations are progressing well and we have substantially completed our sales force expansion," said Dr. Sharon Mates, Chairman and CEO of Intra-Cellular Therapies.

Third Quarter Financial Highlights

Total revenues were $22.2 million for the third quarter of 2021, compared to $7.4 million of total revenues for the third quarter of 2020. Net product revenues of CAPLYTA were $21.6 million for the third quarter of 2021, compared to $7.4 million in net product revenues of CAPLYTA for the same period in 2020.
Cost of product sales were $2.0 million in the third quarter of 2021 compared to $0.6 million for the same period in 2020.
Research and development (R&D) expenses for the third quarter of 2021 were $27.0 million, compared to $10.3 million for the third quarter of 2020. This increase is due to higher lumateperone clinical trial costs and an increase in other development program costs.
Selling, general and administrative (SG&A) expenses were $70.5 million for the third quarter of 2021, compared to $52.5 million for the same period in 2020. This increase is primarily due to an increase in marketing and commercialization costs.
Net loss for the third quarter of 2021 was $76.9 million compared to a net loss of $55.2 million for the same period in 2020.
Cash, cash equivalents, restricted cash and investment securities totaled $478.7 million at September 30, 2021, compared to $658.8 million at December 31, 2020.
COMMERCIAL HIGHLIGHTS

Bipolar depression launch preparations continue to progress, and we have substantially completed our sales force expansion. If approved, we expect to launch CAPLYTA in bipolar depression immediately following U.S. Food and Drug Administration (FDA) approval.
Our hybrid commercialization model, combining virtual and in-person engagements, and our digital marketing initiatives continue to deliver consistent revenue and prescription growth despite COVID-19 disruptions affecting the medical care of patients with schizophrenia.
Third quarter CAPLYTA results reflect continued prescription growth, increasing total prescriptions by 15% versus the second quarter of 2021 and approximately 200% versus the same period in 2020.
CLINICAL HIGHLIGHTS

R&D Day Highlighting Development Programs:

The Company hosted an R&D day highlighting its research and development programs. Presentations and discussions from the Company’s management team and external key opinion leaders described different aspects of our broad pipeline, including our lumateperone, ITI-1284, PDE1 inhibitors and ITI-333 platforms.
Lumateperone:

Bipolar Depression Program: The lumateperone sNDAs 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 are under review by the FDA. The Prescription Drug User Fee Act (PDUFA) target action date is December 17, 2021 for these applications.
Adjunctive MDD program: Patient enrollment has been initiated in global studies 501 and 502. These are Phase 3 double blind, placebo-controlled, 6-week studies evaluating lumateperone 42mg as adjunctive treatment to anti-depressants for patients having an inadequate response to antidepressant therapy. 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.
Mixed Features program: Study 403 is ongoing and is evaluating lumateperone 42mg in patients with MDD and in patients with bipolar depression who exhibit mixed features. We expect to complete this study in the second half of 2022.
Lumateperone Long Acting Injectable (LLAI) formulation: Study ITI-007-025, a Phase 1 single ascending dose study of LLAI, is ongoing. We expect to complete this study later this year.
Publications: Announced the publication of Study 404, a Phase 3 clinical study evaluating lumateperone as monotherapy in patients with bipolar depression. The article titled "Efficacy and Safety of Lumateperone for Major Depressive Episodes Associated with Bipolar I or Bipolar II Disorder: A Phase 3 Randomized Placebo-Controlled Trial," was published online in The American Journal of Psychiatry.
Other Programs:

ITI-1284 program: We have initiated our program for the development of ITI-1284-ODT-SL for the treatment of agitation in patients with probable Alzheimer’s disease. Clinical conduct in this program is expected to commence early in 2022. Studies in dementia-related psychosis and certain depressive disorders in the elderly are planned for the first half of 2022.
Phosphodiesterase type I inhibitor (PDE1) program:
Our Phase 2 clinical program evaluating lenrispodun (ITI-214) in Parkinson’s disease has been initiated, and we expect to commence patient enrollment in the first half of 2022.
We announced four publications highlighting the beneficial effects of PDE1 inhibition with lenrispodun on cardiovascular function in patients with heart failure and in age-related vascular changes in preclinical models associated with stiffening of arteries, vascular endothelial dysfunction, and increased inflammation. In addition, a novel cellular mechanism by which PDE1 stimulates cardiac contraction was described in one of these studies. These findings have broad implications, as cardiovascular dysfunction and inflammation play important roles across multiple chronic and age-related diseases.
ITI-333 program in opioid use disorder: ITI-333 is a novel compound that acts as a partial agonist at mu-opioid (MOP) receptors and as antagonists at the serotonin 5HT2A receptors. At MOP receptors, it acts as a partial agonist signaling through G-protein pathways, but it acts as an antagonist at beta-arrestin pathways. These characteristics and results from early clinical and preclinical models highlight the potential of ITI-333 to address important unmet therapeutic needs in opioid use disorder and pain. 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 fourth quarter 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 3650108. 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 November 9, 2021 Avenue Therapeutics, Inc. (NASDAQ: ATXI) ("Avenue"), a company focused on the development of intravenous ("IV") tramadol for the U.S. market, reported the pricing of an underwritten public offering with gross proceeds to the Company expected to be approximately $2.6 million, before deducting underwriting discounts and commissions and other estimated expenses payable by the Company (Press release, Avenue Therapeutics, NOV 9, 2021, View Source [SID1234595127]). The offering equates to 1,946,787 shares at a price to the public of $1.34 per share. The Company intends to use the net proceeds from this offering for working capital and general corporate purposes.

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In addition, the Company granted the underwriters a 45-day option to purchase additional shares of common stock, representing up to 15% of the number of the shares, solely to cover over-allotments, if any, which would increase the total gross proceeds of the offering to approximately $3 million, if the over-allotment option is exercised in full.

The offering is expected to close on November 12, 2021, subject to the satisfaction of customary closing conditions.

Aegis Capital Corp. is acting as sole book-running manager for the offering.

The securities described above are being offered by Avenue Therapeutics pursuant to an effective registration statement on Form S-3 (No. 333-259850) previously filed with the U.S. Securities and Exchange Commission (the "SEC") and declared effective by the SEC on October 1, 2021. A final prospectus (the "Prospectus") describing the terms of the proposed offering will be filed with the SEC and will be available on the SEC’s website located at View Source Electronic copies of the Prospectus may be obtained, when available, by contacting Aegis Capital Corp., Attention: Syndicate Department, 810 7th Avenue, 18th floor, New York, NY 10019, by email at [email protected], or by telephone at (212) 813-1010. Before investing in this offering, interested parties should read in their entirety the Prospectus and the other documents that the Company has filed with the SEC that are incorporated by reference in such Prospectus, which provide more information about the Company and such offering.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy any securities, nor shall there be any sales of the securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On November 9, 2021 ChemoCentryx, Inc., (Nasdaq: CCXI), reported financial results for the third quarter ended September 30, 2021 and provided an overview of recent corporate highlights (Press release, ChemoCentryx, NOV 9, 2021, View Source [SID1234595126]).

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"TAVNEOS is approved and now launched in the U.S.," said Thomas J. Schall, Ph.D., President and Chief Executive Officer of ChemoCentryx. "With these events, we have begun at last to achieve two of our most foundational aspirations: first, to improve the lives of patients’ who endure with severe disease, and second, to become an integrated biopharmaceutical company which has discovered, developed, and now markets a drug of its own creation. We hope too that the approval of TAVNEOS marks only the beginning of our promise to people living with major unmet medical needs. Our intent is to proceed now with discussions with regulators on how best to move forward TAVNEOS programs in C3G and HS, and we plan to initiate clinical development of TAVNEOS in lupus nephritis this coming year as well. Let’s also remember that our orally administered checkpoint inhibitor CCX559 is now in development for the treatment of cancer. I like to think we have important goals for patients, and a pipeline to match."

Key Highlights and Recent Developments

In October the Company announced FDA approval of TAVNEOS (avacopan) as an adjunctive treatment in adult patients with severe active ANCA-associated vasculitis (or ANCA vasculitis), specifically granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) (the two main forms of ANCA vasculitis), in combination with standard therapy. TAVNEOS is the first orally-administered inhibitor of the complement 5a receptor to be approved by the FDA.
The Company launched TAVNEOS in the United States in October.
ChemoCentryx’s Kidney Health Alliance with Vifor Pharma provides Vifor Pharma with exclusive rights to commercialize TAVNEOS in markets outside of the United States:
In September the Company announced that Kissei Pharmaceutical Co., Ltd. (a sub-licensee of Vifor Pharma) had received approval from the Japanese Ministry of Health, Labor, and Welfare (MHLW) to market TAVNEOS in Japan for the treatment of patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA), the two main forms of ANCA vasculitis.
In November a regulatory opinion is expected in Europe on the use of TAVNEOS in ANCA-associated vasculitis from the Committee for Human Medicinal Products (CHMP).
Data regarding TAVNEOS were presented at the annual meetings of the American College of Rheumatology and the American Society of Nephrology in November. Outcomes from the ADVOCATE trial in ANCA vasculitis demonstrated improvements in kidney function and health-related quality of life in the TAVNEOS group. Also, 52-week results from the ACCOLADE trial in C3G were presented; demonstrating attenuated progression of fibrosis (scarring) in the kidney was evident in the group of patients receiving TAVNEOS in the trial.
The Company plans to meet with the FDA to discuss the Phase III development of TAVNEOS in patients with Hurley Stage 3 (severe) Hidradenitis Suppurativa (HS) with the goal of initiating a Phase III clinical trial in those patients. In the Phase II AURORA trial, TAVNEOS demonstrated a statistically significant higher response than placebo in a pre-specified subgroup of Hurley Stage 3 patients, which will further guide clinical development.
The Company also plans a meeting with the FDA to discuss evidence of clinical benefit from the ACCOLADE trial of TAVNEOS in the very rare disorder C3 Glomerulopathy (C3G), for which there are no FDA approved therapies. In the ACCOLADE trial, TAVNEOS demonstrated statistically significant improvement in renal function as measured by pre-specified secondary endpoints of estimated Glomerular Filtration Rate (eGFR) and also improvement in the pre-specified endpoint of C3G Histology Index (HI) Disease Chronicity score (a measure of fibrotic progression), compared to placebo over 26 weeks of blinded treatment, though not a statistically significant improvement in the primary endpoint of the C3G HI Disease Activity Score (a measure of active inflammation). TAVNEOS was well tolerated in C3G patients.
The Company plans to initiate clinical development of TAVNEOS in patients with lupus nephritis in mid- 2022.
The Company continues to progress its Phase I clinical development of CCX559, a novel, orally-administered, PD-1/PD-L1 checkpoint inhibitor. As a next generation therapy, small molecule checkpoint inhibitors may have advantageous properties compared to approved monoclonal antibodies, such as better penetration into solid tumors, reduced immunogenicity, lack of Fc-mediated side effects, and the convenience of oral administration.
The Company ended Q3 with cash, cash equivalents and investments of approximately $372 million at September 30, 2021.
Third Quarter 2021 Financial Results

Revenue was $17.7 million for the third quarter of 2021, compared to $5.1 million for the same period in 2020. The increase in revenue from 2020 to 2021 was attributable to the $20.0 million milestone from Vifor for the September 2021 JNDA approval by the MHLW, for TAVNEOS in the treatment of ANCA vasculitis.

Research and development expenses were $20.0 million for the third quarter of 2021, compared to $18.6 million for the same period in 2020. The increase from 2020 to 2021 was primarily due to the manufacture of commercial drug supply in anticipation of the launch of TAVNEOS in the treatment of ANCA vasculitis and higher Phase I related expenses associated with the development of CCX559, our orally-administered small molecule checkpoint (PD-1/PD-L1) inhibitor. These increases were partially offset by lower Phase II related expenses due to the completion of the TAVNEOS AURORA Phase IIb clinical trial in patients with HS.

General and administrative expenses were $19.6 million for the third quarter of 2021, compared to $10.4 million for the same period in 2020. The increase from 2020 to 2021 was principally due to higher employee-related expenses, including those associated with our commercialization planning efforts, and higher professional fees.

Net loss for the third quarter of 2021 was $22.3 million, compared to net loss of $24.1 million for the same period in 2020.

Total shares outstanding at September 30, 2021 were approximately 69.9 million shares.

Cash, cash equivalents and investments totaled $371.5 million at September 30, 2021. The Company expects to end the year with cash, cash equivalents and investments in excess of $360 million.

Conference Call and Webcast

The Company will host a conference call and webcast today, November 9, 2021 at 5:00 p.m. Eastern Time / 2:00 p.m. Pacific Time. To participate by telephone, please dial (877) 303-8028 (Domestic) or (760) 536-5167 (International). The conference ID number is 7270887. A live and archived audio webcast can be accessed through the Investors section of the Company’s website at www.ChemoCentryx.com. The archived webcast will remain available on the Company’s website for fourteen (14) days following the call.

INDICATION

TAVNEOS (avacopan) is indicated as an adjunctive treatment of adult patients with severe active anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (granulomatosis with polyangiitis [GPA] and microscopic polyangiitis [MPA]) in combination with standard therapy including glucocorticoids. TAVNEOS does not eliminate glucocorticoid use.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS
Serious hypersensitivity to avacopan or to any of the excipients

WARNINGS AND PRECAUTIONS
Hepatotoxicity: Serious cases of hepatic injury have been observed in patients taking TAVNEOS, including life-threatening events. Obtain liver test panel before initiating TAVNEOS, every 4 weeks after start of therapy for six months and as clinically indicated thereafter. Monitor patients closely for hepatic adverse reactions, and consider pausing or discontinuing treatment as clinically indicated (refer to section 5.1 of the Prescribing Information). TAVNEOS is not recommended for patients with active, untreated and/or uncontrolled chronic liver disease (e.g., chronic active hepatitis B, untreated hepatitis C, uncontrolled autoimmune hepatitis) and cirrhosis. Consider the risk and benefit before administering this drug to a patient with liver disease.

Serious Hypersensitivity Reactions: Cases of angioedema occurred in a clinical trial, including one serious event requiring hospitalization. Discontinue immediately if angioedema occurs and manage accordingly. TAVNEOS must not be re-administered unless another cause has been established.

Hepatitis B Virus (HBV) Reactivation: Hepatitis B reactivation, including life threatening hepatitis B, was observed in the clinical program. Screen patients for HBV. For patients with evidence of prior infection, consult with physicians with expertise in HBV and monitor during TAVNEOS therapy and for six months following. If patients develop HBV reactivation, immediately discontinue TAVNEOS and concomitant therapies associated with HBV reactivation, and consult with experts before resuming.

Serious Infections: Serious infections, including fatal infections, have been reported in patients receiving TAVNEOS. The most common serious infections reported in TAVNEOS group were pneumonia and urinary tract infections. Avoid use of TAVNEOS in patients with active, serious infection, including localized infections. Consider the risks and benefits before initiating TAVNEOS in patients with chronic infection, at increased risk of infection or who have been to places where certain infections are common.

ADVERSE REACTIONS
The most common adverse reactions (≥5% of patients and higher in the TAVNEOS group vs. prednisone group) were: nausea, headache, hypertension, diarrhea, vomiting, rash, fatigue, upper abdominal pain, dizziness, blood creatinine increased, and paresthesia.

DRUG INTERACTIONS
Avoid coadministration of TAVNEOS with strong and moderate CYP3A4 enzyme inducers. Reduce TAVNEOS dose when co-administered with strong CYP3A4 enzyme inhibitors to 30 mg once daily. Monitor for adverse reactions and consider dose reduction of certain sensitive CYP3A4 substrates.

Please see Full Prescribing Information and Medication Guide for TAVNEOS.

About TAVNEOSTM (avacopan)

TAVNEOS (avacopan), approved by the FDA as an adjunctive treatment of ANCA-associated vasculitis, is a first-in-class, orally-administered small molecule that employs a novel, highly targeted mode of action in complement-driven autoimmune and inflammatory diseases. While the precise mechanism in ANCA vasculitis has not been definitively established, TAVNEOS, by blocking the complement 5a receptor (C5aR) for the pro-inflammatory complement system fragment known as C5a on destructive inflammatory cells such as blood neutrophils, is presumed to arrest the ability of those cells to do damage in response to C5a activation, which is known to be the driver of ANCA vasculitis. TAVNEOS’s selective inhibition of only the C5aR is believed to leave the beneficial C5a pathway through the C5L2 receptor functioning normally.

ChemoCentryx is also developing TAVNEOS for the treatment of patients with C3 glomerulopathy (C3G), hidradenitis suppurativa (HS) and Lupus Nephritis (LN). The U.S. Food and Drug Administration granted TAVNEOS orphan drug designation for ANCA-associated vasculitis and C3G. The European Commission has granted orphan medicinal product designation for TAVNEOS for the treatment of two forms of ANCA-associated vasculitis: microscopic polyangiitis and granulomatosis with polyangiitis (formerly known as Wegener’s granulomatosis), as well as for C3G. TAVNEOS has not been approved for indications discussed as in development, and the safety and efficacy of TAVNEOS for those uses has not been established.

About ANCA-Associated Vasculitis

ANCA-associated vasculitis is a systemic disease in which over-activation of the complement pathway further activates neutrophils, leading to inflammation and destruction of small blood vessels. This results in organ damage and failure, with the kidney as the major target, and is fatal if not treated. Currently, treatment for ANCA-associated vasculitis consists of courses of non-specific immuno-suppressants (cyclophosphamide or rituximab), combined with the administration of daily glucocorticoids (steroids) for prolonged periods of time, which can be associated with significant clinical risk including death from infection.

On November 9, 2021 Turning Point Therapeutics, Inc. (NASDAQ: TPTX), a precision oncology company developing next-generation therapies that target genetic drivers of cancer, reported financial results for the third quarter ended September 30, 2021 and provided operational updates (Press release, Turning Point Therapeutics, NOV 9, 2021, View Source [SID1234595125]).

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"We are encouraged by the progress made across our pipeline, including recent preliminary data presented for repotrectinib and elzovantinib at the AACR (Free AACR Whitepaper)-NCI-EORTC meeting," said Athena Countouriotis, M.D., president and CEO. "We look forward to multiple anticipated upcoming FDA interactions including a pre-NDA meeting for repotrectinib in ROS1-positive non-small cell lung cancer."

Third quarter and recent highlights include:

REPOTRECTINIB, ROS1/TRK INHIBITOR

Second Breakthrough Therapy Designation (BTD) granted by the U.S. Food and Drug Administration (FDA) for repotrectinib for the treatment of patients with advanced solid tumors that have an NTRK gene fusion who have progressed following treatment with one or two prior TRK tyrosine kinase inhibitors, with or without prior chemotherapy, and have no satisfactory alternative treatments. BTD is granted by the FDA to expedite the development and regulatory review of an investigational medicine that is intended to treat a serious or life-threatening condition.

The company anticipates discussing next steps towards registration of repotrectinib in patients with NTRK-positive TKI-pretreated advanced solid tumors at a Type B meeting with the FDA in the fourth quarter of 2021.

Progress in the Phase 2 TRIDENT-1 registrational study of repotrectinib, where the company reported early interim data at the AACR (Free AACR Whitepaper)-NCI-EORTC conference. Utilizing an August 26, 2021 data cutoff for the updated Phase 2 dataset and a July 22, 2019 data cutoff for Phase 1, the preliminary efficacy analysis across multiple cohorts pooled from the Phase 1 and Phase 2 portions of the study demonstrated confirmed objective response rates (cORRs) of 39% in ROS1-positive NSCLC patients pretreated with one prior TKI and prior platinum-based chemotherapy (EXP2: n=23); 30% in ROS1-positive NSCLC patients pretreated with two prior TKIs without prior chemotherapy (EXP-3: n=10); 38% in ROS1-positive NSCLC patients pretreated with one prior TKI without prior chemotherapy (EXP-4: n=39); 41% in NTRK-positive TKI-naïve solid tumor patients (EXP-5: n=17); and 48% in NTRK-positive TKI-pretreated solid tumor patients (EXP-6: n=23). The cORRs in patients with solvent front mutations (SFMs) were 53% in ROS1-positive TKI-pretreated NSCLC patients with a G2032R SFM (n=15), and 62% in NTRK-positive TKI-pretreated solid tumor patients with NTRK SFMs (n=13). Phase 2 responses were determined by physician assessment, and Phase 1 responses were determined by blinded independent central review (BICR).

The safety analysis from 301 treated patients from the pooled Phase 1 and Phase 2 portions of TRIDENT-1 across all cohorts demonstrated that repotrectinib was generally well tolerated, with the majority of treatment related adverse events reported as grade 1 or 2.
The company anticipates reporting topline BICR data from all of the ROS1-positive NSCLC cohorts from TRIDENT-1 and discussing the BICR data with the FDA at a pre-NDA meeting, in the second quarter of 2022. The company plans to discuss available BICR data in at least 50 TKI-naïve and 50 TKI-pretreated patients with at least six months of follow-up for the majority of responders.

Progress in the Phase 1/2 CARE study of repotrectinib in pediatric and young adult patients, where the company reported early data at the SIOP Congress. Utilizing an August 2, 2021 data cutoff, the company highlighted preliminary responses by physician assessment and a generally tolerable safety profile. Eight patients were evaluable for efficacy, including four TKI-naïve and four TKI-pretreated patients. Three TKI-naïve patients (two with NTRK fusion solid tumors and one with ROS1 fusion IMT) achieved confirmed responses, including 1 complete response.

ELZOVANTINIB (TPX-0022), MET/SRC/CSF1R INHIBITOR

Progress in the Phase 1 SHIELD-1 study of elzovantinib, Turning Point’s MET, SRC and CSF1R inhibitor, where updated preliminary data from the dose finding portion of the study reported at the AACR (Free AACR Whitepaper)-NCI-EORTC conference highlighted clinical activity, including objective responses across multiple tumor types and a generally tolerable safety profile utilizing an August 23, 2021 data cutoff. Among 11 MET TKI-naïve NSCLC patients, four achieved confirmed responses for a cORR of 36% across all dose levels. Among nine MET TKI-naïve gastric/gastroesophageal junction (GC/GEJ) patients, three achieved confirmed responses for a cORR of 33% across all dose levels. Elzovantinib was generally well tolerated, with the most frequently reported TEAE being dizziness (65%) of which 94% of reported cases were grade 1 or grade 2. Responses were determined by physician assessment.

Completion of an End of Phase 1 Meeting with the FDA focused on next steps in NSCLC, where the design of the planned Phase 2 portion of the SHIELD-1 study and the recommended Phase 2 dose (RP2D) were discussed. The company proposed a RP2D of 40 mg QD to 40 mg BID at the meeting based on available data. The FDA recommended that the company explore an additional intermediate dose level using the QD titration to BID dosing strategy in at least six to 10 patients prior to starting the Phase 2 portion of the study.

Patient screening at the intermediate dose level (60 mg QD to 60 mg BID) is ongoing and the company plans to enroll at least six to 10 patients at this dose level and provide data from this dose level to the FDA, with the intention of revising the SHIELD-1 study into a potentially registrational Phase 1/2 study and initiating the Phase 2 portion in 2022. The company also continues to enroll patients in the Phase 1 dose expansion portion of the study at 40 mg QD to 40 mg BID.

FDA feedback on the development path for elzovantinib in gastric/gastroesophageal junction (GEJ) cancer is anticipated in the fourth quarter of 2021.

The company announced a clinical collaboration with EQRx to evaluate elzovantinib in combination with aumolertinib, EQRx’s drug candidate targeting EGFR, in patients with EGFR mutant MET-amplified advanced NSCLC. The company anticipates initiating the SHIELD-2 combination study of elzovantinib and aumolertinib in mid-2022, pending filing of an investigational new drug (IND) application by the FDA.
TPX-0046, RET INHIBITOR

Progress in the ongoing dose-finding portion of the Phase 1/2 SWORD-1 study, where the company continues to evaluate multiple doses and schedules to further characterize the pharmacokinetics, safety, and efficacy profile before determining the RP2D.

TPX-0131, ALK INHIBITOR

Ongoing patient dosing in the Phase 1/2 FORGE-1 study of TPX-0131 in locally advanced or metastatic TKI-pretreated ALK-positive NSCLC. The study endpoints include safety and tolerability, determination of the recommended Phase 2 dose, pharmacokinetics, and any early signals of efficacy.
DISCOVERY

Continued advancement of four internal discovery programs targeting aberrant GTPase signaling known to drive genomically defined cancers with significant unmet medical need. The most advanced programs target KRAS G12D and the p21 activated kinase, or "PAK" family. Turning Point is targeting 2 development candidates in the second half of 2022 with a goal to achieve at least one new IND per year beginning in 2023.

Third Quarter Financial Results

R&D Expenses: Research and development expenses were $48.9 million in the quarter, compared to $32.2 million in the third quarter of 2020. The $16.7 million increase was primarily driven by the year-over-year increase in investments to develop repotrectinib, elzovantinib, TPX-0046 and TPX-0131, discovery efforts and personnel expenses.

G&A Expenses: General and administrative expenses were $18.2 million compared to $11.3 million in the third quarter of 2020. This increase was primarily due to higher personnel expenses from an increase in head count and professional fees, including those associated with launch readiness.

Net Income/Loss: Net loss was $66.3 million compared to a net loss of $17.7 million for the third quarter of 2020. The net loss in the third quarter of 2020 was partially offset by the $25 million recorded as a result of the upfront payment from Zai Lab under the company’s license agreement for repotrectinib in Greater China.

Cash Position: Cash, cash equivalents and marketable securities at September 30, 2021 totaled approximately $1.0 billion, reflecting a net decrease of $86.5 million in the first three quarters of 2021. Turning Point projects its cash position funds current operations into 2024.
Webcast and Conference Call
Turning Point will webcast its Quarterly Update Conference Call today, November 9 at 4:30 p.m. ET/1:30 p.m. PT. Dr. Countouriotis will host the call, which will be accessible through the "Investors" section of tptherapeutics.com or by dialing (877) 388-2118 (in the United States) or (470) 495-9489 (outside the U.S.) using conference ID 3118428. A replay will be available through the "Investors" section of www.tptherapeutics.com.

On November 9, 2021 Altimmune, Inc. (Nasdaq: ALT), a clinical-stage biopharmaceutical company, reported financial results for the three- and nine-months ending September 30, 2021 and provided a corporate update (Press release, Altimmune, NOV 9, 2021, View Source [SID1234595124]).

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"The third quarter was a momentous time for our pemvidutide (ALT-801) program, as we delivered on positive topline data for the 12-week Phase 1 trial, cleared an IND in non-alcoholic steatohepatitis (NASH) with the FDA and initiated a 12-week Phase 1b study in non-alcoholic fatty liver disease (NAFLD)," remarked Vipin K. Garg, Ph.D., President and Chief Executive Officer at Altimmune. "In addition to the previously announced 12-week data showing double-digit weight loss in the 1.8 mg arm without the need for dose titration, we now have MRI-PDFF data in a subset of subjects with hepatic steatosis, or fatty liver, from that study demonstrating a remarkable reduction in liver fat to undetectable levels after only 6 weeks of pemvidutide treatment. These findings show the potential of pemvidutide in the treatment of both obesity and NASH, and we look forward to sharing the data from our ongoing Phase 1b trial in NAFLD and initiating Phase 2 trials for obesity and NASH in 2022."

Program Highlights:

Pemvidutide1 (ALT-801)

Announced weight loss data from 12-week Phase 1 clinical trial of pemvidutide in overweight and obese subjects

Subjects achieved mean weight losses of 4.9%, 10.3%, and 9.0% at 1.2 mg, 1.8 mg, and 2.4 mg doses, respectively
Once-weekly dosing regimen was well-tolerated without dose titration
Clinically meaningful reductions in serum lipids and blood pressure
No discontinuations due to adverse events
Obesity program advancing towards 48-week Phase 2 trial in the first half of 2022

Investigational New Drug application (IND) for obesity expected to be submitted by year end 2021
48-week Phase 2 obesity study expected to commence in the first half of 2022
1 proposed INN

Reduction in liver fat by MRI-PDFF exploratory analysis in recently completed Phase 1 study

MRI-PDFF data on liver fat content have now been analyzed through 6 weeks of treatment. While the trial inclusion criteria did not pre-specify a minimum liver fat content, the study did enroll a number of subjects with hepatic steatosis or fatty liver, defined as liver fat content greater than or equal to 5%. Five subjects had baseline hepatic steatosis (liver fat content ranging from 5.5 to 19.5%) and received pemvidutide at 1.8 mg or 2.4 mg dose levels. In each of these subjects, liver fat levels fell to undetectable levels within 6 weeks of treatment, representing a greater than 90% reduction in the liver fat content. These findings reinforce the results from preclinical studies of pemvidutide, which demonstrated statistically greater reductions in liver fat than an equivalent dose of semaglutide and confirm the combined beneficial effects of weight loss and glucagon on liver fat metabolism.

Pemvidutide IND application for NASH cleared and enrollment initiated in Phase 1b clinical trial in NAFLD, with topline data expected in the first half of 2022

The Phase 1b, 12-week NAFLD trial is being conducted in the US, with Dr. Stephen A. Harrison serving as Principal Investigator
The study will include diabetic and non-diabetic subjects, with a primary efficacy end point of the change in liver fat as measured by MRI-PDFF, and a key secondary endpoint of weight loss at Week 12
A 52-week biopsy driven Phase 2 NASH trial is expected to follow the conclusion of the NAFLD trial

Additional activities for continued development of pemvidutide

Drug-drug interaction trial of pemvidutide has been initiated in Australia, with results expected in the first half of 2022
A 12-week study to be initiated in Q1 2022 in the US to further characterize safety and pharmacokinetics of pemvidutide in diabetic subjects
HepTcell

Enrollment progressing in international Phase 2 clinical trial in chronic hepatitis B subjects, with topline data expected in the second half of 2022
Study readouts to include virological markers of hepatitis B infection
Financial Results for the Three and Nine Months Ended September 30, 2021

Altimmune had cash, cash equivalents, short-term investments and restricted cash totaling $199.9 million at September 30, 2021 compared to $216.0 million at December 31, 2020.
Revenue was $0.2 million for the three months ended September 30, 2021 compared to $2.9 million in the same period in 2020. The change in revenue quarter over quarter was primarily due to a decrease in MTEC/DoD revenue during the current period due to the timing of clinical trials and development activities for T-COVID.
Research and development expenses were $29.2 million for the three months ended September 30, 2021, compared to $17.0 million in the same period in 2020. The change was primarily the result of increased expenses related to development activities for the Company’s COVID-19 programs, offset by a decrease in the fair value of contingent consideration liability connected with the acquisition and development of pemvidutide.
General and administrative expenses were consistent period-over-period with $4.2 million recognized for the three months ended September 30, 2021 and $4.2 million in the same period in 2020.
Net loss for the three months ended September 30, 2021 was $33.5 million, or $0.81 net loss per share, compared to $17.8 million in the same period in 2020, or $0.54 net loss per share. Net loss for the nine months ended September 30, 2021 was $73.2 million, or $1.79 net loss per share, compared to $38.4 million in the same period in 2020, or $1.74 net loss per share.

Following the conclusion of the call, the webcast will be available for replay on the Investor Relations page of the Company’s website at www.altimmune.com. The Company has used, and intends to continue to use, the IR portion of its website as a means of disclosing material non-public information and for complying with disclosure obligations under Regulation FD.

About Pemvidutide
Pemvidutide (proposed INN, formerly known as ALT-801) is a novel, investigational, peptide-based GLP-1/glucagon dual receptor agonist for obesity and non-alcoholic steatohepatitis (NASH). Altimmune believes the treatment of obesity is the cornerstone of treating NASH and its co-morbidities and views these conditions as significant unmet medical needs.

About HepTcell
HepTcell is a novel immunotherapeutic comprised of nine synthetic peptides representing conserved hepatitis B (HBV) sequences formulated with IC31, a TLR9-based adjuvant from Valneva SE. The HBV-directed peptides are designed to drive T cell responses against all HBV genotypes towards a functional cure for chronic HBV in patients of diverse genetic backgrounds.