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Regulus Therapeutics Reports First Quarter 2022 Financial Results and Recent Updates

On May 12, 2022 Regulus Therapeutics Inc. (Nasdaq: RGLS), a biopharmaceutical company focused on the discovery and development of innovative medicines targeting microRNAs (the "Company" or "Regulus"), reported financial results for the first quarter ended March 31, 2022 and provided a corporate update (Press release, Regulus, MAY 12, 2022, View Source [SID1234614336]).

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"The year is off to a great start as we continue to advance our pipeline, including the recent acceptance of our IND application for RGLS8429. We are thrilled to begin clinical development where we will investigate the safety, tolerability, pharmacokinetics, and preliminary efficacy of RGLS8429 for the treatment of ADPKD," stated Jay Hagan, CEO of Regulus. "We also entered into an exciting research collaboration with Brigham and Women’s Hospital, which will further our understanding into broader applications of miR-155 inhibitors and potentially bring us closer to improving outcomes for Amyotrophic Lateral Sclerosis (ALS) patients. We look forward to providing updates in the coming quarters regarding progress on these fronts."

Program Updates

RGLS8429 for ADPKD: As announced yesterday, the U.S. Food and Drug Administration (FDA) recently accepted the Company’s IND for RGLS8429 for the treatment of ADPKD. The Company plans to initiate a Phase 1 single-ascending dose (SAD) study in healthy volunteers to assess safety, tolerability and pharmacokinetics of RGLS8429. Following the SAD study, the Company plans to initiate a Phase 1b multiple ascending dose (MAD) study in adult patients with ADPKD to assess safety, tolerability and pharmacokinetics of RGLS8429, and to evaluate the dose response of RGLS8429 treatment on ADPKD biomarkers including polycystins, cystic kidney volume (htTKV), and overall kidney function. Top-line data from the healthy volunteer study are expected in the second half of 2022, and top-line biomarker data for the first cohort of RGLS8429-treated patients with ADPKD are expected in the first half of 2023.

Lademirsen (RG-012) for Alport syndrome: In February 2022, the Company announced completion of enrollment by Sanofi in the Phase 2 HERA clinical study evaluating lademirsen for the treatment of adult patients with Alport Syndrome under the Company’s Collaboration and License Agreement with Sanofi. Final data are expected in the first half of 2023 and, if successful, could provide further validation of the Company’s platform technology designed to address genetic kidney diseases and earn the Company a $25 million milestone.

Corporate Highlights

Collaboration Agreement with Brigham and Women’s Hospital: In March 2022, the Company announced a collaboration agreement with the laboratories of Oleg Butovsky, Ph.D., and Howard L. Weiner, M.D., at Brigham and Women’s Hospital to investigate the biologic effects of miR-155 inhibitors in both in vitro and in vivo models of ALS.

Financial Results

Cash Position: As of March 31, 2022, Regulus had $53.9 million in cash and cash equivalents.

Research and Development (R&D) Expenses: Research and development expenses were $3.7 million for the three months ended March 31, 2022, compared to $3.3 million for the same period in 2021. These amounts reflect internal and external costs associated with advancing our clinical and preclinical pipeline.

General and Administrative (G&A) Expenses: General and administrative expenses were $2.9 million for the three months ended March 31, 2022, compared to $2.5 million for the same period in 2021. These amounts reflect personnel-related and ongoing general business operating costs.

Net Loss: Net loss was $6.7 million, or $0.05 per share (basic and diluted), for the three months ended March 31, 2022, compared to $6.0 million, or $0.08 per share (basic and diluted), for the same period in 2021.

Conference Call and Webcast Information:
The Company will host a conference call and live audio webcast today at 5:00 p.m. Eastern Daylight Time to discuss its first quarter 2022 financial results and corporate update. To access the call, please dial (866) 652-5200 (domestic) or (412) 317-6060 (international). To access the telephone replay of the call, dial (877) 344-7529 (domestic) or (412) 317-0088 (international), passcode ID 6812601. The webcast and telephone replay will be archived on the Company’s website at www.regulusrx.com following the call.

About ADPKD

Autosomal Dominant Polycystic Kidney Disease (ADPKD), caused by the mutations in the PKD1 or PKD2 genes, is among the most common human monogenic disorders and a leading cause of end-stage renal disease. The disease is characterized by the development of multiple fluid filled cysts primarily in the kidneys, and to a lesser extent in the liver and other organs. Excessive kidney cyst cell proliferation, a central pathological feature, ultimately leads to end-stage renal disease in approximately 50% of ADPKD patients by age 60. Approximately 140,000 individuals are diagnosed with the disease in the United States alone, with an estimated global prevalence of 4 to 7 million.

About RGLS8429

RGLS8429 is a novel, next generation oligonucleotide designed to inhibit miR-17 and to preferentially target the kidney. Administration of RGLS8429 has shown robust data in preclinical models, where clear improvements in kidney function, size, and other measures of disease severity and has demonstrated a superior pharmacologic profile compared to Regulus’ first generation compound in preclinical studies. The U.S. Food and Drug Administration (FDA) accepted the Company’s IND for RGLS8429 for the treatment of ADPKD.

Nkarta Reports First Quarter 2022 Financial Results and Corporate Highlights

On May 12, 2022 Nkarta, Inc. (Nasdaq: NKTX), a clinical-stage biopharmaceutical company developing engineered natural killer (NK) cell therapies to treat cancer, reported financial results for the first quarter ended March 31, 2022 (Press release, Nkarta, MAY 12, 2022, View Source [SID1234614335]).

"Last month marked an exciting new chapter for Nkarta and the field of cell therapy as we announced positive preliminary data for our co-lead NK cell therapy candidates, NKX101 and NKX1019, validating our best-in-class allogeneic NK cell platform," said Paul J. Hastings, President and CEO of Nkarta. "Independent clinical trials showed early evidence of powerful anti-tumor activity and beneficial safety profiles in patients with two distinct types of relapsed / refractory hematologic malignancies. Early signs of durability and deepening of responses with additional cycles of therapy were observed in both trials, including MRD negativity in patients with AML who received NKX101. Enrollment is underway at higher 3-dose monotherapy regimens of 1.5 billion cells per dose in both dose expansion studies, and Nkarta looks forward to presenting additional data later this year."

NKX101 Clinical Update

On April 25, 2022, Nkarta reported preliminary data from its Phase 1 study evaluating NKX101, an allogeneic, cryopreserved, off-the-shelf cancer immunotherapy candidate that uses NK cells engineered to target NKG2D ligands on cancer cells, as a multi-dose, multi-cycle monotherapy in patients with relapsed / refractory (r/r) acute myeloid leukemia (AML) and higher-risk myelodysplastic syndrome (MDS). As of data cut-off on April 21, 2022, 21 patients had been enrolled and dosed.
Three of five patients with heavily pre-treated AML treated at the higher dose level in a three-dose regimen achieved a complete response (60% CR) with hematologic recovery, with two of the three responses MRD (measurable residual disease) negative.
NKX101 was generally well tolerated. No dose-limiting toxicities were observed. No cytokine release syndrome (CRS), graft-versus-host disease (GvHD), or immune effector cell-associated neurotoxicity syndrome (ICANS) was observed. The most common higher-grade adverse events were myelosuppression and infection, which are common in this patient population following lymphodepletion.
NKX019 Clinical Update

On April 25, 2022, Nkarta reported preliminary data from its Phase 1 study evaluating NKX019, an allogeneic, cryopreserved, off-the-shelf cancer immunotherapy candidate that uses NK cells engineered to target the B-cell antigen CD19, as a multi-dose, multi-cycle monotherapy in patients with r/r B-cell malignancies. As of data cut-off on April 21, 2022, 13 patients had been enrolled and dosed.
Three of six patients treated at the higher dose level in a three-dose regimen showed a complete response (50% CR), including one patient with aggressive diffuse large B cell lymphoma (DLBCL) and one patient with mantle cell lymphoma (MCL).
NKX019 was generally well tolerated. No dose-limiting toxicities were observed. No CRS, GvHD, or neurotoxicity (ICANS) was observed. The most common higher-grade adverse events were myelosuppression, which is common in this patient population following lymphodepletion.
Anticipated Clinical Milestones

As previously announced, Nkarta plans to present additional clinical data in the second half of 2022 from its ongoing dose escalation clinical trials of NKX101 and NKX019. These data would include longer follow-up on previously reported responses as well as safety and activity data from patients being enrolled in the 3-dose monotherapy regimen of 1.5 billion CAR NK cells per dose.
Pipeline and Platform

In April 2022, Nkarta presented preclinical data from its engineered NK cell platform in four posters at the annual meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper). The posters included data on the use of CRISPR/Cas9 genome editing to enhance the ability of NK cells to target CD70 antigen (jointly presented with CRISPR Therapeutics); analytical and translational methods to better understand patterns of response to CAR NK cells; analysis of surface antigen expression in preclinical models of multiple myeloma; and immune masking strategies for extending the persistence of allogeneic cell therapies.
Other Corporate Highlights

In April 2022, Nkarta received approximately $215.5 million in net proceeds from a public offering of its common stock. This amount included the exercise in full by the underwriters of their option to purchase additional shares of common stock.
In March 2022, Nkarta appointed Angela M. Thedinga, MBA, MPH to its Board of Directors. Ms. Thedinga, an experienced manufacturing technology executive, brings extensive operational expertise in supply chain and commercial-scale manufacturing operations.
First Quarter 2022 and Recent Financial Highlights

Cash and Cash Equivalents: As of March 31, 2022, Nkarta had cash, cash equivalents, restricted cash, and short-term investments of $219.1 million. This amount does not include net proceeds of approximately $215.5 million from the public offering of common stock in April 2022.
R&D Expenses: Research and development (R&D) expenses were $19.6 million for the first quarter of 2022. Non-cash stock-based compensation expense included in R&D expense was $1.9 million for the first quarter of 2022.
G&A Expenses: General and administrative (G&A) expenses were $6.5 million for the first quarter of 2022. Non-cash stock-based compensation expense included in G&A expense was $2.2 million for the first quarter of 2022.
Net Loss: Net loss was $26.0 million, or $0.79 per basic and diluted share, for the first quarter of 2022. This net loss includes non-cash charges of $6.7 million that consisted primarily of share-based compensation of $4.1 million.
Financial Guidance

Nkarta expects its current cash and cash equivalents will be sufficient to fund its current operating plan into 2025. This guidance reflects the proceeds received following the April 2022 public offering of common stock.
About NKX101
NKX101 is an allogeneic, cryopreserved, off-the-shelf cancer immunotherapy candidate that uses natural killer (NK) cells derived from the peripheral blood of healthy donors. It is engineered with a chimeric antigen receptor (CAR) targeting NKG2D ligands on tumor cells. NKG2D, a key activating receptor found on naturally occurring NK cells, induces a cell-killing immune response through the detection of stress ligands that are widely expressed on cancer cells. NKX101 is also engineered with membrane-bound form of interleukin-15 (IL15) for greater persistence and activity without exogenous cytokine support. To learn more about the NKX101 clinical trial in adults with AML or MDS, please visit ClinicalTrials.Gov.

About NKX019
NKX019 is an allogeneic, cryopreserved, off-the-shelf cancer immunotherapy candidate that uses natural killer (NK) cells derived from the peripheral blood of healthy adult donors. It is engineered with a humanized CD19-directed CAR for enhanced tumor cell targeting and a proprietary, membrane-bound form of interleukin-15 (IL-15) for greater persistence and activity without exogenous cytokine support. CD19 is a biomarker for normal and malignant B cells, and it is a validated target for B cell cancer therapies. To learn more about the NKX019 clinical trial in adults with advanced B cell malignancies, please visit ClinicalTrials.Gov.

UPDATE — Aadi Bioscience Reports First Quarter 2022 Financial Results and Provides a Corporate Update

On May 12, 2022 Aadi Bioscience, Inc. (NASDAQ: AADI), a biopharmaceutical company focused on developing and commercializing precision therapies for genetically-defined cancers with alterations in mTOR pathway genes, reported financial results for the first quarter of 2022 and provided a corporate update (Press release, Aadi Bioscience, MAY 12, 2022, View Source [SID1234614334]).

"We are very pleased and encouraged by the strong demand for FYARRO since its February 22nd launch despite the ultra-rare nature of advanced malignant PEComa," commented Neil Desai, Ph.D., Founder, President and Chief Executive Officer of Aadi. "A number of factors are believed to have contributed to the sales in Q1 including pent up demand since FYARRO’s approval on November 22, 2021, transition of expanded access and clinical trial patients to the commercial drug, significant physician awareness and favorable reimbursement," he added.

Dr. Desai continued, "Our clinical team has been focused on advancing nab-sirolimus and the first patient was dosed in our PRECISION 1 tumor-agnostic registration-directed trial in March. Based on data recently presented at AACR (Free AACR Whitepaper), TSC1 and TSC2 genetic alterations within tumors represent one of the larger opportunities within targeted oncology. We have also partnered with large community oncology center networks and next generation sequencing (NGS) providers to identify these patient candidates for our trial, which we believe will augment the pace of enrollment in the PRECISION 1 trial. We anticipate initial clinical data to be available in the first half of next year."

Recent and First Quarter 2022 Corporate Highlights

In May, Aadi was granted a product-specific permanent J-code (J9331) for FYARRO that will become effective on July 1, 2022. This code is expected to further facilitate reimbursement for the drug.
Also in May, Aadi announced a partnership with NGS providers and leaders in genomic testing and profiling, including Foundation Medicine, Tempus and others, to assist with identifying patients for its PRECISION 1 trial. Aadi plans to leverage these partnerships and others to expedite patient recruitment and increase physician familiarity with FYARRO.
Aadi announced a poster presentation at the Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper), held April 8-13, 2022 in New Orleans, LA. The project determined the incidence of advanced cancer patients on an annual basis carrying TSC1 or TSC2 alterations and characterized approximately 12,000 patients who may carry "definite impact" mutations (frameshift, nonsense, splice-site mutations and deep deletions). These data confirmed Aadi’s initial projections on the size of the patient population that could be addressed by a potential nab-sirolimus tumor-agnostic therapy. The study also found that TSC1 alterations were most frequent in bladder, kidney, and lung squamous cell cancers, while TSC2 alterations were most frequent in hepatobiliary, ovarian cancers, and soft tissue sarcomas.
In April, Aadi opened an additional office location in Morristown, New Jersey.
In March, Aadi dosed its first patient in its Phase 2 tumor-agnostic registration-directed trial, PRECISION 1, to evaluate nab-sirolimus in adult and adolescent patients 12 years and older with solid tumors harboring pathogenic inactivating alterations in TSC1 or TSC2 genes. The trial consists of two separate arms of 60 patients each for TSC1 or TSC2 alterations. Initial clinical data from PRECISION 1 are expected in the first half of 2023.
In February, Aadi announced the launch and commercial availability of FYARRO (sirolimus protein-bound particles for injectable suspension) (albumin-bound) for intravenous use for the treatment of adult patients with locally advanced unresectable or metastatic malignant PEComa.
Also in February, FYARRO was added to the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines) as the only preferred treatment regimen for malignant PEComa.
First Quarter 2022 Financial Highlights

As of March 31, 2022, cash and cash equivalents totaled $129.8 million, compared to $149.0 million as of December 31, 2021. Based on our current plans, we expect cash and cash equivalents to fund operations into 2024.

For the three months ended March 31, 2022, net product sales were $2.3 million resulting from the launch of FYARRO in February. This compares to $0.1 million of grant revenue during the three months ended March 31, 2021. No grant revenue was recognized during the three months ended March 31, 2022.

Operating expenses for the three months ended March 31, 2022 were $16.1 million compared to $4.2 million for the same period last year.

Selling, general and administrative expenses for the three months ended March 31, 2022 were $9.1 million, an $8.5 million increase over the same period last year. This increase was primarily the result of increased personnel expenses related to the buildout of our commercial operations and infrastructure, as well as increased marketing expenses related to the commercial launch of FYARRO in February 2022.

Research and development expenses for the three months ended March 31, 2022 were $6.8 million, a $3.2 million increase over the same period last year. This increase was primarily the result of increased clinical trial expenses and costs related to the buildout of the organization.

Net loss for the three months ended March 31, 2022 was $13.9 million compared to $5.5 million for the three months ended March 31, 2021.

Conference Call Information:
Individuals may join the webcast online by clicking here or may participate in the live call via telephone by dialing (877) 407-9716 (domestic) or (201) 493-6779 (international) and using conference ID 13729259. A replay of the call will also be available through Aadi’s website within the "Investors & News/Event Calendar" section.

About FYARRO

FYARRO is an mTOR inhibitor indicated for the treatment of adult patients with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumor (PEComa).

Important Safety Information

Contraindication

FYARRO is contraindicated in patients with a history of severe hypersensitivity to sirolimus, other rapamycin derivatives, or albumin.

Warnings and Precautions

Stomatitis

Stomatitis, including mouth ulcers and oral mucositis, occurred in 79% of patients treated with FYARRO, including 18% Grade 3. Stomatitis was most often first reported within 8 weeks of treatment. Based on the severity of the adverse reaction, withhold, resume at reduced dose, or permanently discontinue FYARRO.

Myelosuppression

FYARRO can cause myelosuppression including anemia, thrombocytopenia and neutropenia. Anemia occurred in 68% of patients; 6% were Grade 3. Thrombocytopenia and neutropenia occurred in 35% of patients each. Obtain blood counts at baseline and every 2 months for the first year of treatment and every 3 months thereafter, or more frequently if clinically indicated. Based on the severity of the adverse reaction, withhold, resume at reduced dose, or permanently discontinue FYARRO.

Infections

FYARRO can cause infections. Infections such as urinary tract infections (UTI), upper respiratory tract infections and sinusitis occurred in 59% of patients. Grade 3 infections occurred in 12% of patients, including a single case each of a UTI, pneumonia, skin, and abdominal infections. Monitor patients for infections, including opportunistic infections. Based on the severity of the adverse reaction, withhold, resume at reduced dose, or permanently discontinue FYARRO.

Hypokalemia

FYARRO can cause hypokalemia. Hypokalemia occurred in 44% of patients including 12% Grade 3 events. Monitor potassium levels prior to starting FYARRO and implement potassium supplementation as medically indicated. Based on the severity of the adverse reaction, withhold, resume at reduced dose, or permanently discontinue FYARRO.

Hyperglycemia

FYARRO can cause hyperglycemia. Hyperglycemia occurred in 12% of patients treated with FYARRO, all of which were Grade 3 events. Monitor fasting serum glucose prior to starting FYARRO. During treatment, monitor serum glucose every 3 months in non-diabetic patients, or as clinically indicated. Monitor serum glucose more frequently in diabetic patients. Based on the severity of the adverse reaction, withhold, resume at reduced dose, or permanently discontinue FYARRO.

Interstitial Lung Disease / Non-Infectious Pneumonitis

FYARRO can cause interstitial lung disease (ILD) / non-infectious pneumonitis. ILD / non-infectious pneumonitis occurred in 18% of patients treated with FYARRO, of which all were Grades 1 and 2. Based on the severity of the adverse reaction, withhold, reduce the dose, or permanently discontinue FYARRO.

Hemorrhage

FYARRO can cause serious and sometimes fatal hemorrhage. Hemorrhage occurred in 24% of patients treated with FYARRO, including Grade 3 and Grade 5 events in 2.9% of patients each. Monitor patients for signs and symptoms of hemorrhage. Based on the severity of adverse reaction, withhold, resume at reduced dose, or permanently discontinue FYARRO.

Hypersensitivity Reactions

FYARRO can cause hypersensitivity reactions. Hypersensitivity reactions, including anaphylaxis, angioedema, exfoliative dermatitis, and hypersensitivity vasculitis have been observed with administration of the oral formulation of sirolimus. Hypersensitivity reactions including anaphylaxis have been observed with human albumin administration. Monitor patients closely for signs and symptoms of infusion reactions during and following each FYARRO infusion in a setting where cardiopulmonary resuscitation medication and equipment are available. Monitor patients for at least 2 hours after the first infusion and as clinically needed for each subsequent infusion. Reduce the rate, interrupt infusion, or permanently discontinue FYARRO based on severity and institute appropriate medical management as needed.

Embryo-Fetal Toxicity

Based on animal studies and the mechanism of action, FYARRO can cause fetal harm when administered to a pregnant woman. In animal studies, mTOR inhibitors caused embryo-fetal toxicity when administered during the period of organogenesis at maternal exposures that were equal to or less than human exposures at the recommended lowest starting dose. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to avoid becoming pregnant and to use effective contraception while using FYARRO and for 12 weeks after the last dose.

Male Infertility

Azoospermia or oligospermia may be observed in patients treated with FYARRO. FYARRO is an anti-proliferative drug and affects rapidly dividing cells such as germ cells.

Immunizations and Risks Associated with Live Vaccines

No studies in conjunction with immunization have been conducted with FYARRO. Immunization during FYARRO treatment may be ineffective. Update immunizations according to immunization guidelines prior to initiating FYARRO, if possible. Immunization with live vaccines is not recommended during treatment and avoid close contact with those who have received live vaccines while on FYARRO. The interval between live vaccinations and initiation of FYARRO should be in accordance with current vaccination guidelines for patients on immunosuppressive therapies.

Risk of Transmission of Infectious Agents with Human Albumin

FYARRO contains human albumin, a derivative of human blood. Human albumin carries only a remote risk of transmission of viral diseases because of effective donor screening and product manufacturing processes. A theoretical risk for transmission of Creutzfeldt-Jakob Disease (CJD) also is considered extremely remote. No cases of transmission of viral diseases or CJD have ever been associated with albumin.

Adverse Reactions

Adverse Reactions in PEComa

The most common adverse reactions (≥30%) were stomatitis in 27 (79%) patients; fatigue and rash in 23 (68%) patients each; infection in 20 (59%) patients; nausea and edema in 17 (50%) patients each; diarrhea, musculoskeletal pain and decreased weight in 16 (47%) patients each; decreased appetite in 15 (44%) patients; cough in 12 (35%) patients; and vomiting and dysgeusia in 11 (32%) patients each.

Laboratory Abnormalities in PEComa

The most common Grade 3 to 4 laboratory abnormalities (≥6%) were decreased lymphocytes in 7 (21%) patients; increased glucose and decreased potassium in 4 (12%) patients each; decreased phosphate in 3 (9%) patients; and decreased hemoglobin and increased lipase in 2 (6%) patients each.

Dosage interruptions

Dose interruptions of FYARRO due to an adverse reaction occurred in 22 (65%) patients. Adverse reactions which required dosage interruption in >5% of patients included stomatitis in 6 (18%) patients, pneumonitis in 5 (15%) patients, anemia in 3 (9%) patients, and dehydration, dermatitis acneiform, and thrombocytopenia in 2 (6%) patients each.

Dose reduction

Dose reductions of FYARRO due to an adverse reaction occurred in 12 (35%) patients. Adverse reactions which required dose reductions in > 5% of patients included stomatitis and pneumonitis in 3 (9%) patients each.

Drug Interactions

Reduce the dosage of FYARRO to 56 mg/m2 when used concomitantly with a moderate or weak cytochrome P-450 3A4 (CYP3A4) inhibitor. Avoid concomitant use with drugs that are strong CYP3A4 and/or P-glycoprotein (P-gp) inhibitors and inducers and with grapefruit and grapefruit juice.

Use in Specific Populations

Pregnancy

Based on the mechanism of action and findings in animals, FYARRO can cause fetal harm when administered to a pregnant woman. Advise females of the potential risk to a fetus and to avoid becoming pregnant while receiving FYARRO.

Lactation

Sirolimus is present in the milk of lactating rats. There is potential for serious adverse effects from sirolimus in breastfed infants based on mechanism of action. Because of the potential for serious adverse reactions in breastfed infants from FYARRO, advise women not to breastfeed during treatment with FYARRO and for 2 weeks after the last dose.

Females and Males of Reproductive Potential

FYARRO can cause fetal harm when administered to a pregnant woman. Verify the pregnancy status of females of reproductive potential prior to starting treatment with FYARRO. Advise females of reproductive potential to use effective contraception and avoid becoming pregnant during treatment with and for at least twelve weeks after the last dose of FYARRO. Advise males with female partners of reproductive potential to use effective contraception and avoid fathering a child during treatment with FYARRO and for at least twelve weeks after the last dose of FYARRO. Although there are no data on the impact of FYARRO on fertility, based on available clinical findings with oral formulation of sirolimus and findings in animals, male and female fertility may be compromised by the treatment with FYARRO.

Pediatric

The safety and effectiveness of FYARRO in pediatric patients have not been established.

Geriatric Use

Of the 34 patients treated with FYARRO, 44% were 65 years of age and older, and 6% were 75 years of age and older. Clinical studies of FYARRO did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients.

Hepatic Impairment

FYARRO is not recommended for use in patients with severe hepatic impairment. Reduce FYARRO dosage in patients with mild or moderate hepatic impairment.

Full prescribing information can be found here.

About Malignant PEComa

Advanced malignant PEComa, defined by the World Health Organization as ‘mesenchymal tumors composed of distinctive cells that show a focal association with blood-vessel walls and usually express both melanocytic and smooth muscle markers,’ are a rare subset of soft-tissue sarcomas, with an undefined cell of origin. While there is no formal epidemiology for malignant PEComa, it is estimated that there are about 100-300 new patients per year in the United States. Malignant PEComas may arise in almost any body site (typically the uterus, retroperitoneum, lung, kidney, liver, genitourinary, and gastrointestinal tract with a female predominance) and can have an aggressive clinical course including distant metastases and ultimately death. The estimated prognosis based on retrospective reports is 12-16 months. Cytotoxic chemotherapies typically used for sarcoma show minimal benefit. Malignant PEComas have been shown to frequently harbor mutations in the TSC1 and/or TSC2 genes that result in the activation of mTOR pathway making it a rational therapeutic target for this disease.

About the PRECISION 1 Trial

The PRECISION 1 trial is a multi-center, open-label, tumor-agnostic pivotal study, of nab-sirolimus designed as a basket trial that will evaluate approximately 120 adult and adolescent patients with solid tumors harboring pathogenic inactivating alterations in TSC1 or TSC2 genes. The trial will have two independent arms of 60 patients each to separately evaluate patients with either TSC1 or TSC2 inactivating alterations. Aadi has received Fast Track designation to evaluate nab-sirolimus in this indication from the FDA. The first patient in the PRECISION 1 trial was dosed in March 2022.

About the National Comprehensive Cancer Network (NCCN)
The NCCN is a not-for-profit alliance of 27 leading U.S. cancer centers devoted to patient care, research and education, is dedicated to improving the quality, effectiveness and efficiency of cancer care. The intent of the NCCN Guidelines is to assist in the decision-making process of individuals involved in cancer care – including physicians, nurses, pharmacists, payers, patients and their families – with the ultimate goal of improving patient care and outcomes. For more information about the National Comprehensive Cancer Network go to: View Source

Silverback Therapeutics Reports First Quarter 2022 Financial Results and Provides Business Update

On May 12, 2022 Silverback Therapeutics, Inc. (Nasdaq: SBTX) ("Silverback"), a biopharmaceutical company leveraging its proprietary ImmunoTAC technology platform to develop systemically delivered, tissue targeted therapeutics for the treatment of chronic viral infections, cancer, and other serious diseases, reported financial results for the first quarter ended March 31, 2022 and provided a business update (Press release, Silverback Therapeutics, MAY 12, 2022, View Source [SID1234614333]).

"In the first quarter of 2022, we have made significant progress in advancing the preclinical development of SBT8230, a first-in-class antibody-drug conjugate that we believe has the potential to drive functional cure in patients with chronic hepatitis B (cHBV) by eliciting a liver-localized anti-viral response," said Laura Shawver, Ph.D., chief executive officer of Silverback. "We believe that activating the immune response is an important component of a functional cure and may be combined with treatments that target the HBV life cycle to improve durability. Our team is on track to complete a regulatory submission in the fourth quarter of 2022, enabling the planned initiation of the single ascending dose healthy volunteer cohort of the Phase 1 study in the first quarter of 2023. We plan to report data from this cohort in the second half of 2023."

SBT8230 (ASGR1-TLR8 ImmunoTAC conjugate for chronic HBV)

Initiated Phase 1-enabling toxicology study for SBT8230 in the first quarter of 2022 and on track to complete Phase 1 regulatory submission in the fourth quarter of 2022. Silverback expects to open enrollment for the single ascending dose healthy volunteer cohort of the Phase 1 study in the first quarter of 2023 and anticipates reporting data from this portion of the study in the second half of 2023. SBT8230 is comprised of an ASGR1 monoclonal antibody conjugated to a TLR8 linker-payload. ASGR1 is highly expressed in liver and is restricted in its expression to this organ. SBT8230 is designed to elicit a liver-localized anti-viral immune response and has the potential to improve the therapeutic window observed with untargeted, orally administered TLR8 agonists in cHBV, which have shown promise preclinically, but have been limited by toxicities in the clinic associated with immune activation in the gastrointestinal tract.
ImmunoTAC Discovery Programs

Silverback continues to advance discovery programs, with an update anticipated in the fourth quarter of 2022. Discovery efforts are focused on evaluating and developing new antigen binding domains specific for targets of interest (including antibodies), next-generation linker technologies, and both agonist and antagonist small molecule payloads, that may be combined to create novel tissue-targeted antibody conjugates.
First Quarter Financial Results

For the first quarter ended March 31, 2022, Silverback reported a net loss of $24.6 million, compared to a net loss of $18.9 million for the comparable period in 2021.

Research and development expenses for the first quarter ended March 31, 2022 were $16.9 million, compared to $12.2 million for the same period in 2021. The increase in the Company’s research and development expenses in 2022 were primarily attributable to an increase in direct costs related to preclinical research efforts, including the Company’s SBT8230 program, and increases in personnel-related expenses as operations grew in support of program advances.

General and administrative expenses for the first quarter ended March 31, 2022 were $7.8 million, compared to $6.6 million for the same period in 2021. The increase in general and administrative expenses in 2022 were primarily attributable to an increase in personnel-related expenses, including increases in salaries, bonuses, and stock-based compensation. The increase in general and administrative expenses in 2022 was also due to an increase in legal fees, professional fees, and other various general and administrative expenses as we now operate as a public company.

As of March 31, 2022, Silverback reported cash, cash equivalents, and investments of $298.1 million, compared to $319.1 million at December 31, 2021, which is expected to fund operating expenses and capital expenditure requirements into the second half of 2026. As of March 31, 2022, Silverback had 35,145,281 shares of common stock outstanding.

Spectrum Pharmaceuticals Reports First Quarter 2022 Financial Results and Provides Corporate Update

On May 12, 2022 Spectrum Pharmaceuticals, Inc. (NasdaqGS: SPPI), a biopharmaceutical company focused on novel and targeted oncology therapies, reported that financial results for the three-month period ended March 31, 2022 and provided a corporate update (Press release, Spectrum Pharmaceuticals, MAY 12, 2022, View Source [SID1234614332]).

"We anticipate FDA approvals later this year for poziotinib and eflapegrastim. In the first quarter, we initiated a confirmatory study and presented additional positive scientific data for poziotinib. The resubmitted BLA for eflapegrastim was also accepted for review by the FDA," said Tom Riga, President and Chief Executive Officer of Spectrum Pharmaceuticals. "We are proud of the progress we’ve made toward our core business objectives and we remain dedicated to making a meaningful difference in the lives of cancer patients."

Pipeline Updates

Eflapegrastim, a novel long-acting G-CSF

The U.S. Food and Drug Administration (FDA) has accepted Spectrum’s resubmitted Biologics License Application (BLA) for eflapegrastim with a Prescription Drug User Fee Act (PDUFA) date of September 9, 2022. The company is working with its partner, Hanmi Pharmaceutical, to support the FDA regulatory review process.
Poziotinib, a Pan ErbB inhibitor targeting HER2 exon20 mutations

The New Drug Application (NDA) for poziotinib is under active review at the FDA with Fast Track designation. The NDA is based on the positive results of Cohort 2 in patients with previously treated locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring HER2 exon 20 insertion mutations. The agency has set a PDUFA date of November 24, 2022. There is currently no FDA approved therapy for patients with NSCLC harboring HER2 exon 20 insertion mutations.
A study for poziotinib has been initiated to confirm the clinical benefit seen in Cohort 2, as required for an accelerated approval. The trial, Study SPI-POZ-301 (PINNACLE), is designed to enroll 268 patients with previously treated NSCLC harboring HER2 exon 20 mutations. Patients are being randomized 2-to-1 into one of two treatment arms using 8mg of poziotinib orally administered BID (twice daily) versus 75mg/m2 of docetaxel administered intravenously every three weeks. The primary endpoint will be Progression Free Survival.
FDA’s Oncologic Drugs Advisory Committee (ODAC) is scheduled to review poziotinib for the treatment of patients with previously treated locally advanced or metastatic NSCLC harboring HER2 exon 20 insertion mutations. The fall ODAC meeting is being held September 22-23, 2022. ODAC is an independent panel of experts that evaluates data concerning the efficacy and safety of marketed and investigational products for use in the treatment of cancer and makes appropriate recommendations to the FDA. As usual, the final decision regarding the approval of the product is made by the FDA solely, and the recommendations by the panel are non-binding.
Data from Cohort 4 of the ZENITH20 study in patients with treatment-naïve NSCLC harboring HER2 exon 20 insertion mutations were presented in an oral session at the European Society for Medical Oncology Targeted Anticancer Therapies (ESMO TAT) Congress 2022. The results showed a confirmed objective response rate (ORR) of 41%, as evaluated centrally by an independent image review committee using RECIST 1.1 criteria. The evaluable patient population showed an ORR of 50%. The study met its primary endpoint as the observed lower bound of 30% exceeded the pre-specified lower bound of 20%. The safety profile was consistent with the tyrosine kinase inhibitor (TKI) class. Notably, on-target adverse events (AEs) were meaningfully reduced with BID dosing.
The company presented a poster on the predictive ability of circulating tumor DNA (ctDNA) in poziotinib-treated patients with NSCLC harboring HER2 exon 20 insertion mutations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting. Preliminary results suggest that decreases in plasma ctDNA during poziotinib therapy correlate with clinical response in patients with advanced NSCLC with HER2 exon 20 insertion mutations. Additional data from this study will be presented at the 2022 ASCO (Free ASCO Whitepaper) Annual Meeting in early June.
Corporate Updates

Nora E. Brennan was named Chief Financial Officer effective May 25, 2022. Ms. Brennan has served on Spectrum’s Board of Directors since December 2020 and as Chair of the Audit Committee. She will relinquish her board duties to assume her new senior leadership role. Most recently, Ms. Brennan served as Chief Financial Officer of Fore Biotherapeutics, a developer of cancer therapies driven by functional genomics. Prior to Fore, she served as Chief Financial Officer at TELA Bio, Inc. and as Senior Vice President of Treasury and Investor Relations at Integra Life Sciences Holdings Corporation.
Hanmi Pharmaceutical completed a $20 million strategic equity investment in Spectrum in January 2022, which included revisions to the licensing and supply agreements for eflapegrastim and poziotinib.
Two new members of the Board of Directors have been named. In March, Juhyun Lim was appointed to the Board. Ms. Lim currently serves as President, Global Strategy and Planning at Hanmi Science and Hanmi Pharmaceutical, where she leads the execution of corporate strategy and investment. In May, Spectrum named Brittany Bradrick to the Board and she will succeed Ms. Brennan as Chair of the Audit Committee. Ms. Bradrick currently serves as Chief Financial Officer of Neurelis, Inc. Ms. Bradrick is a seasoned executive with 25 years of experience in the life sciences sector including in the areas of mergers and acquisitions, investment banking, finance, strategy and corporate development.
A strategic restructuring with a ~30% staff reduction and ~20-25% reduction in operating cash burn was initiated in January 2022 to focus the company’s development activities on its late-stage assets, poziotinib and eflapegrastim. Development activities for the early-stage pipeline has been deprioritized.
Three-Month Period Ended March 31, 2022 (All numbers are from Continuing Operations and are approximate)

GAAP Results

Spectrum recorded a net loss of $15.4 million, or a $0.09 loss per basic and diluted share, in the three-month period ended March 31, 2022, compared to a net loss of $35.7 million, or a $0.25 loss per basic and diluted share, in the comparable period in 2021. Total research and development expenses were $4.2 million in the quarter, as compared to $19.4 million in the same period in 2021. Selling, general and administrative expenses were $9.9 million in the quarter, compared to $14.3 million in the same period in 2021.

Non-GAAP Results

Spectrum recorded a non-GAAP net loss of $9.6 million, or a $0.06 non-GAAP loss per basic and diluted share, in the three-month period ended March 31, 2022, compared to a non-GAAP net loss of $29.4 million, or a $0.20 non-GAAP loss per basic and diluted share, in the comparable period in 2021. Non-GAAP research and development expenses were $2.1 million, as compared to $18.0 million in the same period of 2021. Non-GAAP selling, general and administrative expenses were $7.5 million, as compared to $11.5 million in the same period in 2021.

Cash Position and Guidance

In January, the company received a $20 million strategic equity investment from Hanmi Pharmaceutical. Together with this strategic investment, Spectrum ended the quarter with cash, cash equivalents, and marketable securities of approximately $89.2 million. The additional cash, combined with the restructuring, is expected to extend the company’s cash runway into 2023.

This conference call will also be webcast. Listeners may access the webcast, which will be available on the investor relations page of Spectrum Pharmaceuticals’ website: View Source on May 12, 2022 at 4:30 p.m. Eastern/1:30 p.m. Pacific.