On November 2, 2023 Moderna, Inc. (NASDAQ:MRNA) reported financial results and provided business updates for the third quarter of 2023 (Press release, Moderna Therapeutics, NOV 2, 2023, View Source/news/news-details/2023/Moderna-Reports-Third-Quarter-2023-Financial-Results-and-Provides-Business-Updates–" target="_blank" title="View Source/news/news-details/2023/Moderna-Reports-Third-Quarter-2023-Financial-Results-and-Provides-Business-Updates–" rel="nofollow">View Source;/default.aspx [SID1234636819]).

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"Through this quarter, we demonstrated our ability to increase share in the U.S. market, and we now expect this year’s vaccination rate to be similar to last fall," said Stéphane Bancel, Chief Executive Officer of Moderna. "In the third quarter, we significantly resized our manufacturing infrastructure to make our COVID-19 franchise profitable for 2024 and beyond. We are preparing to launch multiple products through 2025, including our RSV vaccine. We expect to return to sales growth in 2025 and, through disciplined investment, to break even in 2026."

Recent progress includes:

2023 Commercial Updates

COVID-19: The Company reported $1.8 billion in Spikevax (COVID-19 vaccine) sales in the third quarter of 2023, which includes $0.9 billion of U.S. sales and $0.8 billion of international sales. This leads to $3.9 billion in vaccine sales for the year through the third quarter. The Company believes that the U.S. market for fall 2023 will be at least 50 million doses, supporting total 2023 Spikevax sales of at least $6 billion. The U.S. fall 2023 vaccinations administered in retail pharmacies to date are tracking similarly to the 2022 fall season, despite a later launch. Spikevax is available in all leading pharmacies and points of care and continues to gain market share. With 45% cumulative market share1 as of the most recently available date in October, Moderna’s market share in the fall 2023 season is tracking ahead of its cumulative market share of 36% during the fall 2022 U.S. vaccination season.

The Company continues to focus on public health efforts to increase vaccination rates globally. In the United States, the Company has undertaken significant marketing and awareness campaigns, working closely with vaccinators and others to drive a robust vaccination season, including by activating the medical community, supporting and re-engaging customers (including those who deferred updated vaccination due to recent infections) and amplifying the voices of credible influencers.

RSV: The Company continues to expect the launch of its RSV vaccine in 2024 with a potential best-in-class profile. Moderna has submitted marketing authorization applications globally for mRNA-1345, a vaccine for the prevention of RSV-associated lower respiratory tract disease (RSV-LRTD) and acute respiratory disease (ARD) in adults aged 60 years or older. The Company filed for a Biologics License Application (BLA) with the FDA and used a Priority Review Voucher (PRV) to accelerate review.

The regulatory applications are based on positive data from the pivotal ConquerRSV study, a randomized, double-blind, placebo-controlled study of approximately 37,000 adults, 60 years or older. The trial met both its primary efficacy endpoints, with a vaccine efficacy (VE) of 83.7% (95.88% CI: 66.1%, 92.2%; p<0.0001) against RSV-LRTD as defined by two or more symptoms, and a VE of 82.4% (96.36% CI: 34.8%, 95.3%; p=0.0078) against RSV-LRTD defined by three or more symptoms. mRNA vaccine technology has a well-established safety and tolerability profile, with over 1 billion COVID-19 doses administered. Most solicited adverse reactions were mild to moderate, and no cases of Guillain-Barre Syndrome (GBS) have been reported with mRNA-1345 in the Phase 3 RSV trial. In addition to older adults, mRNA-1345 is being investigated in a fully enrolled, ongoing Phase 1 trial in pediatric populations.

Moderna is preparing for the marketing launch of mRNA-1345 and believes its U.S. COVID-19 market share to date demonstrates the Company’s ability to compete in the commercial market. The Company is encouraged by early indications of strong consumer awareness and demand in the RSV market. Moderna believes that clinical data for its RSV vaccine supports a best-in-class profile and that its ready-to-use pre-filled syringes (PFS) offer another competitive differentiator over currently licensed products, which require multiple preparatory steps by pharmacists and clinicians. Feedback from clinicians and customers in the COVID-19 market, where Moderna has a similar presentation, validates the benefits of PFS administration. The Company’s pre-launch activities at this time are largely focused on scientific exchanges and public health engagements.

Third Quarter 2023 Financial Results

Revenue: Total revenue for the third quarter of 2023 was $1.8 billion, compared to $3.4 billion in the same period in 2022, mainly due to a decrease in sales of the Company’s COVID-19 vaccine. Net product sales for the third quarter of 2023 were $1.8 billion, a decrease of 44% compared to the same period in 2022, primarily driven by lower sales volume and partially offset by a higher average selling price.

Cost of Sales: Cost of sales for the third quarter of 2023 was $2.2 billion. Moderna has made substantial progress during the quarter in resizing its COVID-19 manufacturing footprint to accelerate gross margin expansion toward its longer-term target of 75-80%. In addition to $0.4 billion in unit driven manufacturing, distribution cost and royalties, the remaining $1.9 billion includes the following charges: $1.3 billion for inventory write-downs related to excess and obsolete COVID-19 product, contract manufacturing wind-down cost of $0.5 billion, and cancellation fees of $0.1 billion. $1.4 billion of these charges were primarily driven by resizing efforts in the third quarter, with an additional $0.2 billion expected in the fourth quarter of 2023.

Research and Development Expenses: Research and development expenses for the third quarter of 2023 increased by 41% to $1.2 billion, in comparison to the same quarter of 2022. The growth in spending was mainly due to an increase in clinical trial-related expenses, largely driven by increased clinical development activities, particularly with respect to the Company’s respiratory and oncology programs.

Selling, General and Administrative Expenses: Selling, general and administrative expenses for the third quarter of 2023 increased by 59% to $442 million, in comparison to the third quarter of 2022. The growth in spending was primarily due to increased personnel-related cost and outside services spend, driven by the build-out of our commercial activities and medical affairs in particular to support the launch of the U.S. commercial market.

Income Taxes: Income taxes for the third quarter of 2023 were $1.7 billion, which is primarily driven by a $1.7 billion non-cash charge related to a valuation allowance on deferred tax assets. This valuation allowance does not impact cash flows, future returns or the Company’s ability to utilize deferred tax assets in future periods.

Net Income (Loss): Net loss was $3.6 billion for the third quarter of 2023, compared to net income of $1.0 billion for the third quarter of 2022, primarily driven by mostly non-cash charges of $3.1 billion related to resizing and tax allowances.

Earnings (Loss) Per Share: Diluted loss per share was $9.53 for the third quarter of 2023, compared to diluted earnings per share of $2.53 for the third quarter of 2022.

Cash, Cash Equivalents and Investments: Cash, cash equivalents and investments were $12.8 billion as of September 30, 2023, down from $14.6 billion as of June 30, 2023, driven by the operating loss in the quarter.

2023 Financial Framework

Product Sales: The Company now expects product sales of at least $6 billion for 2023. The largest remaining variable to sales for the year relates to U.S. vaccination rates, and the estimate assumes trends consistent with the fall 2022 period.

Cost of Sales: The Company now expects cost of sales to be approximately $5 billion for the year, inclusive of charges of approximately $1.6 billion across the third and fourth quarters related to proactive resizing of the Company’s manufacturing footprint. Before the resizing charges of $1.6 billion, costs of sales would be at the lower end of previous guidance range of $3.5 billion to $4 billion.

Respiratory Cost of Sales Framework: The Company’s manufacturing resizing is expected to drive more predictable cost of sales going forward. Write-downs/charges are expected to be less than 10% of sales in 2024 and beyond (74% year to date). Moderna’s resized footprint is now better positioned to scale with volume. At a $4 billion sales level, the Company expects cost of sales of approximately 35%, reducing to approximately 30% at $6 billion of sales and 20-25% at higher sales levels.

Research and Development (R&D) and Selling, General and Administrative (SG&A): The Company now expects full-year 2023 expenses of approximately $6.3 billion (previously $6 billion), with approximately $4.8 billion in R&D (previously $4.5 billion).

Income Taxes: The Company now anticipates a full-year tax expense of approximately $0.8 billion to $1.0 billion, driven by an increase in valuation allowance on deferred tax assets (previously a benefit of ~$0.7-1.0 billion). This valuation allowance does not impact cash flows, future returns or the Company’s ability to utilize deferred tax assets in future periods.

Capital Expenditures: The Company expects capital expenditures for 2023 of approximately $0.9 billion (previously $1.0 billion).

Moderna Operating Principles

The Company expects its COVID-19 franchise to be profitable in its anticipated sales scenarios for 2024 and beyond. While Moderna plans to continue to invest in its business to drive an unparalleled opportunity for organic sales growth, the Company will be disciplined and will adjust its investments in R&D and SG&A based on its sales performance. Moderna expects to break even in 2026 through product launches and disciplined investments. The Company’s current balance sheet is sufficient to fund its planned investments without raising additional equity.

Early Thoughts on 2024 and 2025 Sales

Moderna is projecting approximately $4 billion in sales in 2024, mostly in the second half of the year, primarily due to COVID-19 vaccine global sales and the launch of its RSV vaccine. In 2025, the Company expects to return to organic sales growth. The Company is projecting cost of sales as a percentage of sales to be approximately 35% in 2024, which is expected to improve with sales increasing in 2025. R&D expenses are expected to be approximately $4.5 billion in 2024 and flat to down in 2025. SG&A expenses are expected to be approximately $1.3 billion in 2024 and flat to down in 2025. Taxes are expected to be negligible in both 2024 and 2025. The Company expects capital expenditures to be approximately $0.9 billion in 2024 and materially lower in 2025, following the completion of manufacturing sites in Australia, Canada and the United Kingdom. Moderna expects to break even in 2026. The Company expects an ending cash balance of approximately $9 billion in 2024 and in the range of $6 billion to $7 billion in 2025.

Clinical Updates

Moderna’s mRNA platform is positioned to continue to deliver significant impact with our mRNA medicines. The Company is anticipating up to 15 launches in the next five years and provided a comprehensive overview of its pipeline and clinical programs at R&D Day in September. Moderna currently has therapeutics in development across four therapeutic areas, with a total of 43 development programs. Other notable updates are provided below.

Respiratory : Moderna has advanced three respiratory disease programs to positive Phase 3 data (COVID-19, RSV, Influenza).

Moderna also recently announced positive interim results from the Phase 1/2 trial of mRNA-1083, an investigational combination vaccine against seasonal influenza and COVID-19. Moderna’s investigational combination vaccines are designed to deliver value to individuals, providers and healthcare systems through higher compliance, easier administration and greater convenience.

The ongoing Phase 1/2 clinical trial (ClinicalTrials.gov Identifier: NCT05827926) is a randomized, observer blind study evaluating the safety and immunogenicity of mRNA-1083 compared to a standard dose influenza vaccine, Fluarix, in adults 50-64 years of age and against an enhanced influenza vaccine, Fluzone HD, in adults 65-79 years of age. For both age groups, mRNA-1083 was compared against Spikevax booster.

The Company also recently announced that it has initiated a Phase 3 trial of mRNA-1083 in 2023 and is targeting initial regulatory approval for the combination vaccine in 2025. The Phase 3 study will evaluate the immunogenicity, safety, and reactogenicity of mRNA‐1083 as compared with active control, co‐administered licensed influenza and SAR‐CoV‐2 vaccines in 8,000 healthy adults 50 years of age or older.

mRNA‐1083 has the potential to efficiently reduce the overall burden of acute viral respiratory diseases by providing simultaneous protection against influenza and SARS‐CoV‐2 viruses in a single injection. mRNA‐1083 offers greater convenience and has the potential to lead to increased compliance with vaccine recommendations. This approach could benefit public health by synergistically increasing coverage rates against influenza and SARS‐CoV‐2 viruses.

Latent: The pivotal Phase 3 study of Moderna’s CMV vaccine candidate (mRNA-1647), known as CMVictory, is fully enrolled including an adolescent cohort. The trial evaluates the efficacy, safety and immunogenicity of mRNA-1647 in the prevention of primary infection in women of childbearing age.

INT: In April 2023, Moderna and Merck reported the results from the Phase 2b KEYNOTE-942/mRNA-4157-P201 trial evaluating mRNA-4157 (V940), an investigational individualized neoantigen therapy (INT), in combination with KEYTRUDA, Merck’s anti-PD-1 therapy, in patients with resected high-risk melanoma (stage III/IV). In the overall intention-to-treat population, adjuvant treatment with mRNA-4157 (V940) in combination with KEYTRUDA demonstrated a statistically significant and clinically meaningful improvement in recurrence-free survival (RFS) and reduced the risk of recurrence or death by 44% (HR=0.56 [95% CI, 0.309-1.017]; one-sided p value=0.0266) compared with KEYTRUDA alone. In June, the Company announced a statistically significant and clinically meaningful improvement in distant metastasis-free survival from the Phase 2b KEYNOTE-942/mRNA-4157-P201 trial. mRNA-4157-P201/KEYNOTE-942 is the first randomized trial to demonstrate improvement in recurrence-free survival and distant metastasis-free survival with an individualized neoantigen therapy approach. The Company expects to provide additional data from the Phase 2 study in the fourth quarter of 2023.

Merck and Moderna announced the initiation of a pivotal Phase 3 study (V940-001) to evaluate the safety and efficacy of mRNA-4157 (V940) in combination with KEYTRUDA in people with resected high-risk (Stage IIB-IV) melanoma compared to KEYTRUDA alone. The primary endpoint of the study is recurrence-free survival, and secondary endpoints include distant metastasis-free survival, overall survival and safety. That trial is underway globally.

The Companies will also imminently commence a Phase 3 trial in non-small cell lung cancer (NSCLC) in patients with resected stage II-IIIB NSCLC who have received adjuvant chemotherapy, with no recurrence. The primary endpoint is disease free survival compared to pembrolizumab. Secondary endpoints are overall survival, distant metastasis-free survival, and safety. The trial is expected to enroll approximately 868 patients.

Moderna and Merck plan to expand the INT development program to additional tumor types.

Moderna is scaling manufacturing to support clinical development and commercial markets. The Company is also currently building a manufacturing site in Marlborough, MA as a commercial INT manufacturing facility.

Corporate Updates

Moderna announced strategic partnerships with Immatics and CARsgen
Moderna announced positive clinical results across cancer, rare disease and infectious disease at its 8th annual R&D Day
Company Accolades:

Moderna was ranked as one of the top employers in the global biopharmaceutical industry by Science and Science Careers’ 2023 Top Employers Survey (ninth consecutive year on the list)
Moderna was named to the Boston Business Journal’s annual list of the Most Charitable Companies in Massachusetts (first year on the list)
Moderna was recognized as a top-scoring company on the Disability: IN’s Disability Equality Index (second consecutive year on the list)
Key 2023 Investor and Analyst Event Dates

Digital Day: November 8
ESG Day: December 7
Investor Call and Webcast Information

Moderna will host a live conference call and webcast at 8:00 a.m. ET on November 2, 2023. To access the live conference call via telephone, please register at the link below. Once registered, dial-in numbers and a unique pin number will be provided. A live webcast of the call will also be available under "Events and Presentations" in the Investors section of the Moderna website.

Telephone: https://register.vevent.com/register/BI9ee4891809624391a5618bb9e2ca440f
Webcast: View Source
The archived webcast will be available on Moderna’s website approximately two hours after the conference call and will be available for one year following the call.

On November 2, 2023 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported a poster presentation on the initial Phase 1b clinical data for ORIC-533 in patients with relapsed/refractory multiple myeloma at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting to be held December 9-12, 2023, in San Diego, CA (Press release, ORIC Pharmaceuticals, NOV 2, 2023, View Source [SID1234636816]).

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Details of the ASH (Free ASH Whitepaper) poster presentation are as follows:

Title: Preliminary Results of the Oral CD73 Inhibitor, ORIC-533, in
Relapsed/Refractory Multiple Myeloma (RRMM)
Abstract #: 4761
Session Name: 653. Multiple Myeloma: Prospective Therapeutic Trials: Poster III
Session Date: Monday, December 11, 2023
Presentation Time: 6:00 PM – 8:00 PM PT
Location: San Diego Convention Center, Halls G-H

Abstract Highlights

ORIC-533 is a highly potent and selective, orally bioavailable, small molecule inhibitor of CD73, currently being evaluated in an ongoing Phase 1b dose escalation study to determine its safety, tolerability, and pharmacokinetics and selection of the recommended Phase 2 dose in patients with relapsed/refractory multiple myeloma. The study included a heavily pretreated patient population where all patients were triple-class refractory, 88% were penta-refractory, and 59% also received prior anti-BCMA/CD3 bispecific therapy or anti-BCMA CAR-T therapy. ORIC-533 was well tolerated with the vast majority of treatment-related adverse events (TRAEs) Grade 1 or 2 in severity and with no dose limiting toxicities, no Grade ≥ 4 TRAEs, and no treatment-related serious adverse events. ORIC-533 demonstrated good bioavailability and a plasma half-life of ~24 hours. Strong inhibition of soluble CD73 enzymatic activity was seen across all dose levels. Preliminary evidence of enhanced CD8+ T-cell activation was seen at the highest dose levels tested in both the peripheral blood and bone marrow, and early evidence of single agent clinical activity was observed. Overall, ORIC-533 demonstrated an acceptable safety profile and preliminary evidence of immune activation in this heavily pretreated patient population.

Full abstracts are available for online viewing via the ASH (Free ASH Whitepaper) Annual Meeting website at Hematology.org.

About ORIC-533

ORIC-533 is a highly potent, orally bioavailable small molecule inhibitor of CD73, a key node in the adenosine pathway believed to play a central role in resistance to chemotherapy and immunotherapy-based treatment regimens. ORIC-533 has demonstrated greater potency in preclinical studies compared to an antibody approach, as well as other small molecule inhibitors of CD73 and adenosine receptor antagonists. Preclinical data demonstrated that ORIC-533 binds CD73 with high affinity and effectively blocks adenosine-driven immunosuppression in a high AMP environment, reflective of AMP levels observed in tumors. In preclinical studies, nanomolar concentrations of ORIC-533 efficiently rescued cytotoxic T-cell function in the presence of high AMP concentrations, as well as in ex vivo bone marrow aspirates from relapsed or refractory multiple myeloma patients.

On November 2, 2023 Kura Oncology, Inc. (NASDAQ: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, and Mirati Therapeutics, Inc. (NASDAQ: MRTX), a commercial-stage targeted oncology company, reported a clinical collaboration and supply agreement to evaluate the combination of KO-2806, a next-generation farnesyl transferase inhibitor (FTI), and adagrasib, a highly selective KRASG12C inhibitor, in patients with KRASG12C-mutated non-small cell lung cancer (NSCLC) (Press release, Kura Oncology, NOV 2, 2023, View Source [SID1234636815]).

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"Recent findings suggest that combining KO-2806 with adagrasib can drive tumor regressions and enhance both duration and depth of antitumor response in preclinical models of KRASG12C-mutated NSCLC," said Stephen Dale, M.D., Chief Medical Officer of Kura Oncology. "This collaboration highlights the potential to address the urgent need for more durable and effective treatment options for patients with advanced solid tumors, and we look forward to collaborating with Mirati, an established leader in targeted oncology."

"We are pleased to collaborate with Kura Oncology on this clinical study of KO-2806 with adagrasib. Preclinical work demonstrates the ability of adagrasib, in combination with a FTI, to improve patient outcomes," said Alan Sandler, M.D., Chief Medical Officer, Mirati Therapeutics. "This collaboration exemplifies the potential combinability of adagrasib as a key differentiation from other KRASG12C inhibitors."

Under the terms of the agreement, Kura will sponsor the Phase 1 study of KO-2806 and adagrasib in patients with KRASG12C-mutated NSCLC. Mirati will supply Kura with adagrasib for the study.

About KO-2806

KO-2806 is a next-generation inhibitor of farnesyl transferase designed to improve upon potency, pharmacokinetic and physicochemical properties of earlier FTI drug candidates. Earlier this year, Kura received FDA clearance of its Investigational New Drug application for KO-2806. In addition to KRASG12C NSCLC, KO-2806 has demonstrated encouraging preclinical activity in clear cell renal cell carcinoma (ccRCC). The Company recently dosed the first patients in a Phase 1 dose-escalation trial of KO-2806 (FIT-001). Concurrent with dose escalation as a monotherapy, Kura also plans to evaluate KO-2806 in dose-escalation combination cohorts with other targeted therapies in advanced solid tumors, including adagrasib in KRASG12C-mutated NSCLC and a tyrosine kinase inhibitor in ccRCC.

About Adagrasib

Adagrasib is being evaluated as monotherapy and in combination with other anti-cancer therapies in patients with advanced KRASG12C-mutated solid tumors, including NSCLC, colorectal cancer, and pancreatic cancer. For more information, visit Mirati.com/science.

KRAZATI (adagrasib) U.S. Indication

KRAZATI is indicated for the treatment of adult patients with KRASG12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy.

This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of a clinical benefit in a confirmatory trial(s). For Prescribing Information, visit Mirati.com/KRAZATI_USPI.

KRAZATI (adagrasib) Important Safety Information

WARNINGS AND PRECAUTIONS

Gastrointestinal Adverse Reactions

In the pooled safety population, serious gastrointestinal adverse reactions observed were gastrointestinal obstruction in 1.6%, including 1.4% grade 3 or 4, gastrointestinal bleeding in 0.5% of patients, including 0.5% grade 3, and colitis in 0.3%, including 0.3% grade 3. In addition, nausea, diarrhea, or vomiting occurred in 89% of 366 patients, including 9% grade 3. Nausea, diarrhea, or vomiting led to dosage interruption or dose reduction in 29% of patients and permanent discontinuation of KRAZATI in 0.3%
Monitor and manage patients using supportive care, including antidiarrheals, antiemetics, or fluid replacement, as indicated. Withhold, reduce the dose, or permanently discontinue KRAZATI based on severity
QTc Interval Prolongation

KRAZATI can cause QTc interval prolongation, which can increase the risk for ventricular tachyarrhythmias (eg, torsades de pointes) or sudden death
In the pooled safety population, 6% of 366 patients with at least one post-baseline electrocardiogram (ECG) assessment had an average QTc ≥501 ms, and 11% of patients had an increase from baseline of QTc >60 msec. KRAZATI causes concentration-dependent increases in the QTc interval
Avoid concomitant use of KRAZATI with other products with a known potential to prolong the QTc interval. Avoid use of KRAZATI in patients with congenital long QT syndrome and in patients with concurrent QTc prolongation
Monitor ECGs and electrolytes prior to starting KRAZATI, during concomitant use, and as clinically indicated in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, and in patients who are taking medications that are known to prolong the QT interval. Withhold, reduce the dose, or permanently discontinue KRAZATI, depending on severity
Hepatotoxicity

KRAZATI can cause hepatotoxicity
In the pooled safety population, hepatotoxicity occurred in 37%, and 7% were grade 3 or 4. A total of 32% of patients who received KRAZATI had increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST); 5% were grade 3 and 0.5% were grade 4. Increased ALT/AST leading to dose interruption or reduction occurred in 11% of patients. KRAZATI was discontinued due to increased ALT/AST in 0.5% of patients
Monitor liver laboratory tests (AST, ALT, alkaline phosphatase, and total bilirubin) prior to the start of KRAZATI, and monthly for 3 months or as clinically indicated, with more frequent testing in patients who develop transaminase elevations. Reduce the dose, withhold, or permanently discontinue KRAZATI based on severity
Interstitial Lung Disease /Pneumonitis

KRAZATI can cause interstitial lung disease (ILD)/pneumonitis, which can be fatal. In the pooled safety population, ILD/pneumonitis occurred in 4.1% of patients, 1.4% were grade 3 or 4, and 1 case was fatal. The median time to first onset for ILD/pneumonitis was 12 weeks (range: 5 to 31 weeks). KRAZATI was discontinued due to ILD/pneumonitis in 0.8% of patients
Monitor patients for new or worsening respiratory symptoms indicative of ILD/pneumonitis (eg, dyspnea, cough, fever). Withhold KRAZATI in patients with suspected ILD/pneumonitis and permanently discontinue KRAZATI if no other potential causes of ILD/pneumonitis are identified
Adverse Reactions

The most common adverse reactions (≥25%) are nausea, diarrhea, vomiting, fatigue, musculoskeletal pain, hepatotoxicity, renal impairment, edema, dyspnea, decreased appetite
Females and Males of Reproductive Potential

Infertility: Based on findings from animal studies, KRAZATI may impair fertility in females and males of reproductive potential
Please see Full Prescribing Information.

On November 2, 2023 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, reported third quarter 2023 financial results and provided a corporate update (Press release, Kura Oncology, NOV 2, 2023, View Source [SID1234636814]).

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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"I am proud of our team’s considerable progress, as we continue to execute across all three of our wholly owned, clinical-stage programs," said Troy Wilson, Ph.D., J.D., President and Chief Executive Officer of Kura Oncology. "We believe our lead drug candidate, ziftomenib, is well positioned for market leadership, with multibillion dollar global revenue potential in acute leukemias and beyond. Our conviction is supported by a growing body of clinical data as a monotherapy and, increasingly, in combination with standards of care. We continue to be encouraged by the rapid pace of enrollment in our KOMET-001 registration-directed trial in NPM1-mutant acute myeloid leukemia (AML), as well as in our KOMET-007 combination trial. We look forward to sharing preliminary combination data in NPM1-mutant and KMT2A-rearranged AML early next quarter."

"Meanwhile," continued Dr. Wilson, "we continue to unlock the substantial therapeutic and commercial value of farnesyl transferase inhibition. We believe the positive results from our AIM-HN registration-directed trial of tipifarnib and the favorable safety and tolerability profile of tipifarnib in combination with alpelisib in our ongoing KURRENT-HN trial significantly de-risk development of our next-generation farnesyl transferase inhibitor (FTI), KO-2806. We are pleased to be in the clinic with KO-2806 and look forward to evaluating it in combination with other targeted therapies, including adagrasib in KRASG12C-mutated non-small cell lung cancer (NSCLC) and cabozantinib in clear cell renal cell carcinoma (ccRCC). If successful, we believe KO-2806 could become an ideal combination partner for multiple targeted therapies in large solid tumor indications."

Recent Highlights

Rapid pace of enrollment continues in registration-directed trial of ziftomenib in NPM1-mutant AML – The KOMET-001 registration-directed trial of ziftomenib in NPM1-mutant relapsed or refractory AML is expected to enroll a total of 85 patients in the U.S. and Europe, with a primary endpoint of complete remission (CR) or CR with partial hematologic recovery (CRh). In the Phase 1 trial, ziftomenib demonstrated a 35% CR rate and 45% overall response rate in 20 patients with NPM1-mutant AML treated at the recommended Phase 2 dose. NPM1-mutant AML accounts for approximately 30% of new AML cases annually and represents a disease of significant unmet need for which no approved targeted therapy exists. Kura expects to complete enrollment of all 85 patients in the Phase 2 registration-directed trial no later than mid-2024.
Preliminary data from KOMET-007 combination trial of ziftomenib upcoming – KOMET-007 is a Phase 1 dose-escalation study designed to assess safety, tolerability and preliminary activity of ziftomenib in combination with either: 1) venetoclax and azacitidine in patients with relapsed/refractory NPM1-mutant and KMT2A-rearranged AML or 2) standard induction cytarabine/daunorubicin chemotherapy (7+3) in NPM1-mutant and KMT2A-rearranged patients in the frontline setting. The Company expects to share preliminary data from 20 patients in KOMET-007, including NPM1-mutant and KMT2A-rearranged patients treated with ziftomenib in the newly diagnosed and relapsed/refractory AML settings, early in the first quarter of 2024.
Positive results from AIM-HN registration-directed trial of tipifarnib in HRAS mutant HNSCC – Kura recently presented positive results from the AIM-HN registration-directed trial of tipifarnib as a monotherapy in patients with HRAS mutant head and neck squamous cell carcinoma (HNSCC). The results were featured during a late-breaking mini-oral session at the European Society for Medical Oncology Congress in Madrid. The Company continues to evaluate whether the combination of tipifarnib and alpelisib has potential to extend the clinical benefit observed in the AIM-HN trial to a broader set of HNSCC patients in its ongoing KURRENT-HN study.
First patient dosed in FIT-001 dose-escalation study of KO-2806 – Last month, Kura announced that the first patient was dosed in its FIT-001 Phase 1 dose-escalation trial of KO-2806. KO-2806 is a next-generation FTI designed to improve upon potency, pharmacokinetic and physicochemical properties of earlier FTI drug candidates. Concurrent with dose escalation as a monotherapy in the FIT-001 trial, the Company also plans to evaluate KO-2806 in dose-escalation combination cohorts with adagrasib in KRASG12C-mutated NSCLC and with cabozantinib in ccRCC.
Preclinical data supports clinical combinations of KO-2806 with adagrasib and cabozantinib – Kura presented preclinical data at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) supporting its rationale to combine KO-2806 with adagrasib in KRASG12C-mutated NSCLC and with cabozantinib in ccRCC. The new findings illustrate the potential for FTIs to drive enhanced antitumor activity and address mechanisms of innate and adaptive resistance to targeted therapies such as KRAS inhibitors and tyrosine kinase inhibitors.
Clinical collaboration with Mirati to evaluate KO-2806 and adagrasib in KRASG12C-mutated NSCLC – Earlier today, Kura announced a clinical collaboration and supply agreement with Mirati Therapeutics to evaluate the combination of KO-2806 and adagrasib in patients with KRASG12C-mutated NSCLC. Under the terms of the agreement, Kura will sponsor the Phase 1 study and Mirati will supply adagrasib for the study. The collaboration highlights the potential to address the urgent need for more durable and effective treatment options for patients with cancers driven by the KRASG12C-mutant oncogene.
Brian Powl appointed as Chief Commercial Officer – Mr. Powl joined Kura in August 2023 with more than two decades of experience in building commercial brands in hematology and oncology, with expertise in developing and executing patient-focused strategies across sales, marketing and market access for global biotech and pharmaceutical products, including extensive global experience in hematologic malignancies.
Financial Results

Research and development expenses for the third quarter of 2023 were $29.3 million, compared to $25.0 million for the third quarter of 2022.
General and administrative expenses for the third quarter of 2023 were $13.1 million, compared to $11.6 million for the third quarter of 2022.
Net loss for the third quarter of 2023 was $38.6 million, compared to a net loss of $35.5 million for the third quarter of 2022. This includes non-cash share-based compensation expense of $7.1 million, compared to $6.4 million for the same period in 2022.
As of September 30, 2023, Kura had cash, cash equivalents and short-term investments of $452.6 million, compared to $438.0 million as of December 31, 2022.
Based on its operating plan, management expects that cash, cash equivalents and short-term investments will fund current operations to mid-2026.
Forecasted Milestones

Report preliminary data from 20 patients in the KOMET-007 trial of ziftomenib in combination with venetoclax and azacitidine or 7+3 early in the first quarter of 2024.
Dose the first patients in the KOMET-008 trial of ziftomenib in combination with additional standards of care, including the FLT3 inhibitor gilteritinib, in the first quarter of 2024.
Initiate the ziftomenib post-transplant maintenance program in the first quarter of 2024.
Complete enrollment of 85 patients in the KOMET-001 registration-directed trial of ziftomenib in NPM1-mutant AML by mid-2024.
Determine the optimum biologically active dose for tipifarnib in combination with alpelisib and determine next steps for the program by mid-2024.
Dose the first patients in the FIT-001 dose-escalation trial of KO-2806 in combination with adagrasib in KRASG12C-mutated NSCLC by mid-2024.
Dose the first patients in the FIT-001 dose-escalation trial of KO-2806 in combination with cabozantinib in ccRCC by mid-2024.
Conference Call and Webcast

Kura’s management will host a webcast and conference call at 4:30 p.m. ET / 1:30 p.m. PT today, November 2, 2023, to discuss the financial results for the third quarter 2023 and to provide a corporate update. The live call may be accessed by dialing (888) 886-7786 for domestic callers and (416) 764-8658 for international callers and entering the conference ID: 34983466. A live webcast and archive of the call will be available online from the investor relations section of the company website at www.kuraoncology.com.

On November 2, 2023 Lisata Therapeutics, Inc. (Nasdaq: LSTA) ("Lisata" or the "Company"), a clinical-stage pharmaceutical company developing innovative therapies for the treatment of advanced solid tumors and other serious diseases, reported its financial results for the third quarter ended September 30, 2023 (Press release, Caladrius Biosciences, NOV 2, 2023, View Source [SID1234636812]).

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"Momentum we established during the first half of the year continued during the third quarter with the achievement of several milestones related to ongoing and planned clinical studies of our lead investigational product, LSTA1," stated David J. Mazzo, Ph.D., President and Chief Executive Officer of Lisata. "For example, LSTA1 is now the recipient of multiple orphan drug designations including pancreatic cancer in both the U.S. and Europe, as well as malignant glioma in the U.S. Additionally, as we recently announced, we have successfully treated the first patient in each of the head and neck squamous cell carcinoma and cholangiocarcinoma cohorts of the BOLSTER trial ("BOLSTER"), and we expect a steady uptake in enrollment over the coming quarters. In September, we announced that the ASCEND study ("ASCEND") in Australia received a positive outcome from the planned interim futility analysis by the study’s Independent Data Safety Monitoring Committee ("IDSMC"), which recommended continuation of the study without modification. We are also happy to report that full enrollment in Cohort A of ASCEND has been achieved and that overall enrollment in the study is now approximately 95% complete. With that, we now expect that we could have topline data from Cohort A as early as the fourth quarter of 2024, a full year earlier than originally anticipated. We intend to use the results of the ASCEND trial to explore possible conditional approvals in several jurisdictions and to design an optimized Phase 3 program in Pancreatic Ductal Adenocarcinoma ("PDAC"). Finally, the iLSTA study, done in collaboration with WARPNINE in Australia, a foundation dedicated to accelerating the development of treatments for gastrointestinal cancers, is enrolling rapidly."
Dr. Mazzo continued, "With continued careful management of capital, we reiterate that our expected cash runway projects into early 2026, funding each of our trials through to data. We believe we remain well-positioned to focus on the execution of our development plans and achieve our goal of getting to meaningful clinical data readouts as soon as possible."

Development Portfolio Highlights

LSTA1 as a treatment for solid tumor cancers in combination with other anti-cancer agents
LSTA1 is an investigational drug designed to activate a novel uptake pathway that allows co-administered or tethered (i.e., molecularly bound) anti-cancer drugs to target and penetrate solid tumors more effectively. LSTA1 actuates this active transport system in a tumor-specific manner, resulting in systemically co-administered anti-cancer drugs more efficiently penetrating and accumulating in the tumor, while normal tissues are not expected to be affected. In preclinical models, LSTA1 has also shown the ability to modify the tumor microenvironment, thereby making tumors more susceptible to immunotherapies and inhibiting the metastatic cascade (i.e., the spread of cancer to other parts of the body). Lisata and its development collaborators have amassed significant non-clinical data demonstrating enhanced delivery of a range of existing and emerging anti-cancer therapies, including chemotherapeutics, immunotherapies, and RNA-based therapeutics. To date, LSTA1 has also demonstrated favorable safety, tolerability and activity in completed

and ongoing clinical trials designed to test its ability to enhance delivery of standard-of-care chemotherapy for pancreatic cancer. Currently, LSTA1 is the subject of multiple ongoing or planned Phase 1b/2a and 2b clinical studies being conducted globally in a variety of solid tumor types in combination with a variety of anti-cancer regimens. These studies include:

•ASCEND: Phase 2b double-blind, randomized, placebo-controlled clinical trial evaluating LSTA1 in patients with metastatic Pancreatic Ductal Adenocarcinoma ("mPDAC"). The trial is being conducted at up to 40 sites in Australia and New Zealand led by the Australasian Gastro-Intestinal Trials Group in collaboration with the University of Sydney and with the National Health and Medical Research Council Clinical Trial Centre at the University of Sydney as the Coordinating Centre. Planned interim futility analysis by the IDMC received a positive outcome. Cohort A has been fully enrolled. Total enrollment completion is projected for the second quarter of 2024; however, current total enrollment is at approximately 95% of target, so earlier total enrollment completion may be achieved.
•BOLSTER: Phase 2a double-blind, placebo-controlled, multi-center, randomized basket trial in the U.S., Europe, Canada, and Asia evaluating LSTA1 in combination with standards of care in advanced solid tumors including head and neck, esophageal and cholangiocarcinoma. Enrollment is open and proceeding as planned. First patients have been treated in head and neck cancer as well as cholangiocarcinoma cohorts.
•CENDIFOX: Phase 1b/2a open-label trial in the U.S. of LSTA1 in combination with neoadjuvant FOLFIRINOX based therapies in pancreatic, colon and appendiceal cancers. The trial continues to make steady progress with enrollment completion expected by the fourth quarter of 2023 and data readouts expected in 2024.
•LSTA1 is currently being evaluated in combination with gemcitabine and nab-paclitaxel in a Phase 1b/2a open-label trial in China led by Qilu Pharmaceutical. During the 2023 ASCO (Free ASCO Whitepaper) Annual Meeting, Qilu Pharmaceutical presented an abstract sharing preliminary data from the study which, thus far, has corroborated previously reported findings from the phase 1b/2a trial of LSTA1 plus gemcitabine and nab-paclitaxel conducted in Australia in patients with mPDAC. Final data is expected by the end of the second quarter of 2024.
•iLSTA: Phase 1b/2a randomized, single-blind, single-center, safety and pharmacodynamic trial in Australia evaluating LSTA1 in combination with the checkpoint inhibitor, durvalumab, plus standard-of-care chemotherapy, nab-paclitaxel, and gemcitabine, versus standard-of-care alone in patients with locally advanced non-resectable PDAC. Enrollment completion is expected by the end of the second quarter of 2024.
•The Company will soon initiate the study of LSTA1 in combination with temozolomide in Glioblastoma Multiforme ("GBM"). This study is designed as a Phase 2a double-blind, placebo-controlled, randomized, proof-of-concept study evaluating LSTA1 when added to standard of care ("SoC") temozolomide versus temozolomide and matching LSTA1 placebo in subjects with newly diagnosed GBM. It will be conducted across multiple sites in Estonia and Latvia and is targeted to enroll 30 patients with a randomization of 2:1 LSTA1 + SoC versus Placebo + SoC. Target for the first patient treated is in the fourth quarter of 2023. Importantly and as the Company recently announced, LSTA1 has been granted orphan drug designation by the U.S. FDA for malignant glioma. This action by the FDA not only highlights the unmet medical need but also recognizes the potential of LSTA1 to benefit patients in this indication.
•Lisata will also soon initiate a study of LSTA1 in combination with HIPEC interoperative intraperitoneal lavage in peritoneal carcinomatosis, a condition which develops as a result of the contiguous spread of primary cancers such as ovarian, colorectal and appendiceal along the peritoneum. The study is a Phase I single-center, unblinded, randomized controlled trial to determine the safety and tolerability of LSTA1 administered intraperitoneally in patients with peritoneal metastases from colorectal, appendiceal, or ovarian cancer undergoing Cytoreductive Surgery ("CRS") and HIPEC. Twenty-one total participants will be randomized 2:1 to receive LSTA1 with HIPEC versus HIPEC alone after CRS. We anticipate the first patient treated to be in the fourth quarter of 2023.

Third Quarter 2023 Financial Highlights

Research and development expenses were approximately $3.4 million for the three months ended September 30, 2023, compared to $3.3 million for the three months ended September 30, 2022, representing an increase of $45,000 or 1.3%. Expenses this quarter were primarily due to study activities associated with the BOLSTER trial, enrollment activities for the ASCEND study, startup activities for the LSTA1 GBM study and chemistry, manufacturing and control activities for LSTA1 to support all development activities.
General and administrative expenses were approximately $2.6 million for the three months ended September 30, 2023, compared to $4.0 million for the three months ended September 30, 2022, representing a decrease of $1.4 million or 35.3%. This was primarily due to non-recurring merger related costs in the prior year, a decrease in equity expense due to prior year performance stock unit vesting, merger option assumption expense, departing board member restricted stock unit vesting and timing of our annual stockholder meeting versus the prior year.
Overall, net losses were $5.3 million for the three months ended September 30, 2023, compared to $37.4 million for the three months ended September 30, 2022. Excluding the in-process research and development expense of $30.4 million relating to our merger with Cend Therapeutics in September 2022, net losses for the three months ended September 30, 2023 decreased by $1.7 million or 24.7% compared to the three months ended September 30, 2022.

Balance Sheet Highlights

As of September 30, 2023, the Company had cash, cash equivalents and marketable securities of approximately $54.4 million. Based on its current expected capital needs, the Company believes that its projected capital will fund its current proposed operations into early 2026, encompassing anticipated data milestones from all its ongoing and planned clinical trials.

Conference Call Information

Lisata will hold a live conference call on Thursday, November 2, 2023, at 4:30 p.m. Eastern time to discuss financial results, provide a business update and answer questions.
Those wishing to participate must register for the conference call by way of the following link: CLICK HERE TO REGISTER. Registered participants will receive an email containing conference call details with dial-in options. To avoid delays, we encourage participants to dial into the conference call fifteen minutes ahead of the scheduled start time.
A live webcast of the call will also be accessible under the Investors & News section of Lisata’s website and will be available for replay beginning two hours after the conclusion of the call for 12 months.