On November 12, 2024 Erasca, Inc. (Nasdaq: ERAS), a clinical-stage precision oncology company singularly focused on discovering, developing, and commercializing therapies for patients with RAS/MAPK pathway-driven cancers, reported business updates and reported financial results for the fiscal quarter ended September 30, 2024 (Press release, Erasca, NOV 12, 2024, View Source [SID1234648169]).

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"We made significant progress across our pipeline programs and are pleased with the pace of our execution. Positive preliminary data from SEACRAFT-1, which we reported at the 36th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) (ENA) Symposium last month, has refined our clinical development focus of naporafenib plus trametinib on patients with NRAS-mutant (NRASm) melanoma, and importantly, heightens our conviction in the ongoing SEACRAFT-2 registrational trial targeting a similar patient population," said Jonathan E. Lim, M.D., Erasca’s chairman, CEO, and co-founder. "SEACRAFT-2 has the potential for approval based on the high unmet need of these patients as well as the alignment with US and European regulators on the NRASm melanoma indication. We expect randomized dose optimization data from Stage 1 of this Phase 3 trial in 2025."

Dr. Lim added, "Our RAS targeting franchise, which includes a potential best-in-class pan-RAS molecular glue ERAS-0015 and a potential first-in-class pan-KRAS inhibitor ERAS-4001, holds significant promise to help a broad range of patients with RAS-mutant (RASm) solid tumors. Following the in-licensing of these molecules in May, we have rapidly and effectively confirmed in-house the potential best-in-class profiles of both agents and executed across multiple activities to support their planned investigational new drug (IND) application submissions, which remain on track for the first quarter of 2025 for ERAS-4001 and the first half of 2025 for ERAS-0015. We continue to be well capitalized with an anticipated cash runway into the first half of 2027 and are poised for strong execution across our pipeline."

Research and Development (R&D) Highlights

•
Presented Promising SEACRAFT-1 Phase 1 Data: In October 2024, Erasca presented Phase 1b SEACRAFT-1 data for naporafenib plus trametinib (MEKINIST) in patients with locally advanced unresectable or metastatic solid tumor malignancies with RAS Q61X mutations at the 36th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) (ENA) Symposium on Molecular Targets and Cancer Therapeutics and as part of a company R&D update. Data support rationale for pursuing an NRASm melanoma indication and reinforces the potential of the ongoing Phase 3 SEACRAFT-2 registrational trial.
•
Announced Progress Across RAS Targeting Franchise: In October 2024, Erasca presented a program update for pan-RAS molecular glue ERAS-0015 and pan-KRAS inhibitor ERAS-4001 as part of a company R&D update, highlighting the rapid progress across both programs including in-house
confirmation of potential best-in-class profiles for both agents and advancement of activities to support planned IND application submissions.
Key Upcoming Milestones

•
SEACRAFT-2: Randomized pivotal Phase 3 trial for naporafenib plus trametinib in patients with NRASm melanoma
o
Phase 3 Stage 1 randomized dose optimization data expected to be reported in 2025
•
AURORAS-1: Phase 1 trial for ERAS-0015 (pan-RAS molecular glue) in patients with RASm solid tumors
o
IND filing expected in H1 2025
o
Initial Phase 1 monotherapy data in relevant tumor types expected to be reported in 2026
•
BOREALIS-1: Phase 1 trial for ERAS-4001 (pan-KRAS inhibitor) in patients with KRASm solid tumors
o
IND filing expected in Q1 2025
o
Initial Phase 1 monotherapy data in relevant tumor types expected to be reported in 2026

On November 12, 2024 Cyclacel Pharmaceutical, a biopharmaceutical company developing innovative medicines, reported third quarter financial results and provided a business update (Press release, Cyclacel, NOV 12, 2024, View Source [SID1234648168]).

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"We were pleased to report initial safety and efficacy data from twelve patients with advanced solid tumors enrolled in the Phase 2 part of the 065-101, proof of concept, clinical study of fadraciclib as a single agent as a poster presentation at the 2024 EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) 36th Symposium on Molecular Targets and Cancer Therapeutics ("Triple Meeting"), in Barcelona, Spain. The patients were enrolled in the biomarker-enriched, Cohort 8 of the study and were preselected for CDKN2A and/or CDKN2B abnormalities," said Spiro Rombotis, President and Chief Executive Officer. "Nasdaq has granted the Company an extension until December 24, 2024, to regain compliance with Nasdaq’s minimum stockholders’ equity requirement and we continue to pursue opportunities to obtain additional funding for our programs. If we do not secure such additional funding in an amount that allows us to meet or exceed Nasdaq’s minimum stockholders’ equity requirement, our securities will be delisted from Nasdaq."

Financial Highlights

As of September 30, 2024, cash equivalents totaled $3.0 million, compared to $3.4 million as of December 31, 2023. Net cash used in operating activities was $6.6 million for the nine months ended September 30, 2024 compared to $12.2 million for the same period of 2023. The Company estimates that its available cash will fund currently planned programs into the fourth quarter of 2024.

Although the Company has made substantial reductions in its expenses, there remains substantial doubt about our ability to continue as a going concern. We are currently investigating ways to raise additional capital through private equity financing or by entering into a strategic transaction. In the event that we are not able to secure such additional funding, we may be forced to curtail operations, delay or stop ongoing development activities, cease operations altogether, and/or file for bankruptcy. In such events, our stockholders may lose their entire investment in the Company.

Research and development (R&D) expenses were $1.0 million for the three months ended September 30, 2024, as compared to $5.2 million for the same period in 2023. R&D expenses relating to fadraciclib were $0.9 million for the three months ended September 30, 2024, as compared to $3.6 million for the same period in 2023 due to manufacturing costs not recurring in 2024. R&D expenses related to plogosertib were $0.1 million for the three months ended September 30, 2024, as compared to $1.5 million for the same period in 2023 also due to manufacturing costs not recurring in 2024.

General and administrative expenses for the three months ended September 30, 2024 were $1.2 million, as compared to $1.6 million for the same period in 2023 due largely to reduction in stock compensation costs.

Total other income, net, for the three months ended September 30, 2024 was $10,000 compared to an income of $145,000 for the same period of the previous year.

United Kingdom research & development tax credits for the three months ended September 30, 2024 were $0.2 million compared to $0.7 million for the same period of the previous year. Research & development tax credits are directly correlated to qualifying research and development expenditure.

Net loss for the three months ended September 30, 2024 was $2.0 million, compared to $6.0 million for the same period in 2023.

On November 12, 2024 CureVac N.V. (Nasdaq: CVAC) ("CureVac"), a global biopharmaceutical company developing a new class of transformative medicines based on messenger ribonucleic acid ("mRNA"), reported financial results for the third quarter and first nine months of 2024 and provided a business update (Press release, CureVac, NOV 12, 2024, View Source [SID1234648167]).

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Commenting on the quarter Dr. Alexander Zehnder, Chief Executive Officer of CureVac said:

"The third quarter was truly transformative for CureVac. By restructuring our collaboration with GSK, we have embarked on a new chapter of growth and innovation, unveiling new programs that leverage our advanced mRNA technology to tackle critical health challenges. The strategic decisions we’ve made, combined with encouraging initial clinical results, have laid a solid foundation for our future success. We are now strategically aligned, more operationally efficient, and financially empowered to create shareholder value by advancing our portfolio of novel mRNA-based medicines."

Selected Business Updates

Strategic Redesign

CureVac made meaningful progress in restructuring its operations during the third quarter by implementing significant cost-cutting measures. These include the previously announced 30% workforce reduction, which is on track to be completed by the end of 2024. The goal of the restructuring is to reorganize the company for flexibility in executing immediate priorities while maintaining a strong innovation focus and ensuring long-term value creation. Right-sizing CureVac for future growth allows for continued focused development of a prioritized portfolio, including high-value mRNA projects in oncology, infectious diseases and other areas.

"With funding secured into 2028, and our operational expenses increasingly streamlined by our ongoing redesign, we are in a strong position to expand our R&D efforts across several promising areas," said Dr. Zehnder. "We will be launching new development programs in the coming quarters and will continue to execute our business and pipeline strategy well into the future."

Strengthening the Leadership Team

As of November 11, 2024, CureVac welcomed a new Chief Financial Officer, Axel Sven Malkomes. Mr. Malkomes brings over three decades of senior corporate and investment banking experience within the biotech and pharmaceutical industries. Most recently, he served as CFO at Cardior Pharmaceuticals, a private clinical-stage company developing non-coding RNA-based therapeutics for heart disease. During his tenure, he played a crucial role in strategically and financially preparing the company for capital markets, co-leading financing rounds, and supporting potential M&A and partnering transactions, culminating in the successful acquisition of Cardior by Novo Nordisk in 2024.

Before Cardior, Mr. Malkomes was CFO and Chief Business Officer at Medigene AG, a publicly listed cell therapy company. His extensive experience also includes senior healthcare investment banking roles at Barclays and Société Générale, as well as co-heading European healthcare investments at 3i Group plc, a UK-listed private equity firm with over $20 billion in assets under management. Earlier in his career, he held senior leadership positions at Merck KGaA.

Oncology

Expanding oncology development pipeline

CureVac sees significant opportunities to apply precision immunotherapy using mRNA vaccines in large patient populations. The company aims to create earlier treatment options for multiple solid tumor types and is strengthening its clinical development pipeline following two complementary approaches: off-the-shelf cancer vaccines targeting tumor antigens shared across different patient populations and/or tumor types and fully personalized cancer vaccines based on a patient’s individual tumor genomic profile.

CureVac is extending its off-the-shelf cancer vaccine pipeline and has selected an additional clinical candidate for a shared-antigen cancer vaccine targeting squamous non-small cell lung cancer (sqNSCLC). Investigational New Drug (IND) and Clinical Trial Application (CTA) submissions are being prepared for filing in the first half of 2025. Additional discovery work aims to deliver further off-the-shelf cancer vaccines and selection of a second clinical candidate is anticipated in 2026.

In parallel, the program for fully personalized cancer vaccines is progressing and on track with the planned start of a Phase 1 study expected in the second half of 2026.

Clinical off-the-shelf program in glioblastoma

CureVac presented the first clinical data from the Phase 1 study of CVGBM, its off-the-shelf mRNA cancer vaccine candidate, in patients with resected glioblastoma in September 2024 at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress and in November at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) and the Society for Neuro-Oncology (SNO) Congresses. Preliminary immunogenicity results in this highly aggressive and challenging cancer indication demonstrate the potential of CureVac’s proprietary second-generation mRNA backbone to enhance the immune system’s capacity for a coordinated defense against the disease.

"As our lead oncology program, CVGBM has demonstrated encouraging initial clinical results in patients with resected glioblastoma," said Dr. Myriam Mendila, Chief Scientific Officer of CureVac. "Data presented recently at the ESMO (Free ESMO Whitepaper), SITC (Free SITC Whitepaper) and SNO congresses showed that 77% of evaluable patients exhibited sustained immune response induction over a 99-day monitoring period. Importantly, we believe these data are very promising because the response was led by de novo T-cell generation, which likely plays a crucial role in the success of a cancer vaccine."

In the fully enrolled dose-escalation Part A, CVGBM monotherapy induced cancer antigen-specific T-cell responses in 77% of 13 evaluable patients. Notably, 84% of these immune responses were generated de novo, inducing T-cell activity in patients without prior immunity to the encoded antigens. Among responding patients, 69% showed CD8+ responses, 31% had CD4+ responses, and 23% had both. 67% of responding patients showed immune responses against multiple antigens. At the recommended 100 µg dose for the expansion part of the study, responses were sustainable over a 99-day monitoring period. Induction of cellular responses was accompanied by systemic cytokine and chemokine activation, indicating innate immune response activation.

The treatment was well tolerated, with no dose-limiting toxicities up to the highest dose of 100 µg. 91% of treatment-related adverse events (TRAEs) were mild to moderate systemic reactions characteristic of mRNA-based therapeutics, resolving within 1-2 days post-injection. Seven patients reported nine severe TRAEs, including four serious adverse events; no grade 4 or 5 adverse events occurred.

The dose-expansion Part B of the study is ongoing at the recommended 100 µg dose. Initial data and a decision on advancing the program to Phase 2 are expected in the second half of 2025.

More information can be found at clinicaltrials.gov (NCT05938387).

Prophylactic Vaccines

Initiation of Urinary Tract Infections Program

CureVac has initiated a new program to address urinary tract infections (UTIs), which are among the most common bacterial infections. UTIs are most commonly caused by uropathogenic Escherichia coli (UPEC) bacteria, which can enter the urinary tract, invade and colonize bladder and kidney tissues. These infections can lead to complications such as kidney damage and urosepsis. UTIs lead to approximately 8-10 million doctor office visits and 1-3 million emergency department visits per year in the U.S. alone.

"Urinary tract infections are extremely common, affecting millions of people each year—often repeatedly—and are increasingly prone to antibiotic resistance," said Dr. Mendila. "Our encouraging preclinical data show that our investigational vaccine candidates targeting uropathogenic Escherichia coli elicit strong antibody titers and robust T-cell responses, comparing very favorably to recombinant protein-based vaccines. Based on these promising results, we believe there is a significant commercial opportunity for an mRNA solution that offers meaningful benefits to individuals suffering from these infections."

mRNA technology is ideally suited for developing prophylactic vaccines against bacterial targets like UPEC due to its ability to target specific disease antigens and flexibly combine multiple antigens.

CureVac has conducted preclinical studies with several UPEC vaccine candidates and selected a lead candidate for further preclinical testing. The promising data, which compares favorably to recombinant protein-based vaccines, is being presented at the 12th International mRNA Health Conference in Boston from November 11-14, 2024.

The studies assessed two mRNA vaccine candidates encoding FimH, an antigen facilitating UPEC adhesion to bladder epithelial cells, in mouse and rat models. Both candidates induced high levels of binding antibodies in serum and urine, correlating with high serum functional antibodies, and showed strong induction of antigen-specific CD8+ and CD4+ T-cells. Additionally, both vaccine candidates demonstrated superior immunogenicity compared to protein-based comparator vaccines.

Based on these encouraging preclinical results, CureVac expects to select a clinical candidate in the first half of 2025. An IND application filing is planned in the second half of 2025, aiming to initiate a Phase 1 study in the first half of 2026.

Seasonal Influenza Phase 2 Data – Program Licensed to GSK

In September 2024, GSK announced positive Phase 2 headline data from its seasonal influenza mRNA vaccine program based on CureVac’s second-generation mRNA backbone. According to GSK, the data demonstrated positive immune responses against both influenza A strains as well as historically challenging influenza B strains compared to the current standard of care.The interim data met all predefined success criteria in the tested age groups of older and younger adults and suggested an acceptable safety and reactogenicity profile. GSK confirmed that the program is progressing to Phase 3 in 2025, which will be associated with a significant milestone payment for CureVac.

More information can be found at clinicaltrials.gov (NCT06431607).

As previously announced in July 2024, CureVac and GSK restructured their collaboration into a new licensing agreement. Under the new agreement, GSK has assumed full control of the development, manufacturing and global commercialization of mRNA vaccine candidates against influenza and COVID-19, including combinations. All vaccine candidates currently in clinical development are based on CureVac’s proprietary second-generation mRNA backbone.

Financial Update for the Third Quarter and First Nine Months of 2024

Commenting on the financial results, Axel Sven Malkomes, CureVac’s new Chief Financial Officer, said:

"Joining CureVac at this pivotal time is incredibly exciting. Our strengthened cash position, supported by our strategic redesign—including a significant reduction in headcount—provides a solid foundation to execute our strategic objectives. By extending our cash runway into 2028, we can allocate more resources toward our promising R&D pipeline in oncology and infectious diseases. I am committed to ensuring that we maintain financial discipline as we drive forward our mission to develop transformative mRNA medicines and create long-term value for our shareholders."

Cash Position

Cash and cash equivalents amounted to €550.9 million at the end of September 2024, increasing from €402.5 million at the end of 2023. The company received the €400 million upfront payment from the new GSK licensing agreement in August 2024. In the first nine months of 2024, cash used in operations was mainly allocated to payments related to the termination of raw material commitments for the first-generation COVID-19 vaccine, CVnCoV, amounting to a total of €52 million and the payment of contract manufacturing organization (CMO)-related arbitration awards. All CMO-related arbitrations are closed, with the last payment made in the third quarter of 2024. Looking forward, there will be no further payments related to CVnCoV.

The remaining cash spend was mainly related to ongoing R&D activities. The company reaffirms its expected cash runway into 2028.

Revenues

Revenues amounted to €493.9 million and €520.7 million for the three and nine months ended September 30, 2024, respectively, representing an increase of €477.4 million and €489.5 million, or 2,897% and 1,569%, from €16.5 million and €31.2 million for the same periods in 2023.

The increase year-on-year was primarily driven by the new license agreement with GSK, which was closed in July 2024. CureVac received a non-refundable upfront payment of €400 million. Under the new license agreement, CureVac has no obligation to perform R&D work in connection with the newly granted licenses and GSK is provided with the right to use CureVac’s intellectual property. As such, the upfront payment was fully recognized in the third quarter of 2024 as revenue.

Under previous GSK agreements, upfront and milestone payments were related to R&D activities performed by CureVac over a period of time. Accordingly, related payments were recognized as contract liabilities and recognized as revenue on a pro rata basis over the period R&D activities were performed.

CureVac and GSK agreed in the new license agreement that all unfulfilled performance obligations from prior collaborations relating to R&D services had expired. As a result, the remaining €80.4 million of contract liabilities for prior collaborations were recognized as non-cash revenue in the third quarter of 2024.

€480.4 million of the revenue recognized in the third quarter of 2024 must therefore be seen as a positive one-time event that will not be repeated in the future.

Additionally, in the third quarter of 2024, CureVac reached a development milestone of €10.0 million under the previous GSK collaboration for the Phase 2 transition of the pre-pandemic avian influenza (H5N1) program, which is also fully recognized as revenue in the third quarter of 2024.

The remaining revenues relate to work on the GSK and CRISPR collaborations.

Operating Result

Operating profit amounted to €368.4 million and €221.4 million for the three and nine months ended September 30, 2024, respectively, representing an increase of €422.4 million and €407.6 million from an operating loss of €54.0 million and €186.2 million for the same periods in 2023.

The operating result was affected by several key drivers partially related to the new strategy and the closing of the first-generation vaccine effort in COVID-19:

• Cost of sales increased year-on-year mainly due to higher arbitration costs for CMO activities related to the first-generation COVID-19 vaccine as well as due to higher personnel expenses related to the restructuring of the organization.

• Research and development expenses increased primarily with increased activity in oncology R&D projects. Additionally, the first nine months of 2024 were impacted by increased expenses related to the litigation to enforce intellectual property rights.

• General and administrative expenses decreased compared to the prior year period mainly driven by lower personnel expenses.

• Other income increased year-on-year due to the sale of raw materials to GSK.

• Other operating expenses increased year-on-year due to a partial impairment of CureVac’s production facility.

While the production facility was initially planned and set up for commercial (large scale) production, CureVac no longer has large scale production obligations in addition to the strategic re-focus on technology innovation, research and development. Most parts of the production process can be scaled down to provide products for clinical production. Parts of the production process that cannot be scaled down were partially impaired in an amount of €36.6 million.

Financial Result (Finance Income and Expenses)

Net financial result for the three and nine months ended September 30, 2024, amounted to €2.2 million and €8.0 million, or a decrease of €3.1 million and €4.7 million, from €5.3 million and €12.7 million, respectively, for the same periods in 2023. This decrease was mainly driven by lower interest income on cash investments.

Pre-Tax Results

Pre-tax profit was €370.6 million and €229.4 million for the three and nine months ended September 30, 2024, compared to a pre-tax loss of €48.7 million and €173.5 million in the same periods of 2023.

Conference call and webcast details

CureVac will host a conference call and webcast today at 3 p.m. CET / 9 a.m. EST.
Dial-in numbers to participate in the conference call:

U.S. Toll-Free: +1-877-407-0989
International: +1-201-389-0921
Germany: 0800-182-0040 (landline access) / 0800-184-4713 (cell phone access)

The live webcast link can be accessed via the newsroom section of the CureVac website at View Source

Corresponding presentation slides will be posted shortly before the start of the webcast.

A replay will be made available at this website after the event. • General and administrative expenses decreased compared to the prior year period mainly driven by lower personnel expenses.

• Other income increased year-on-year due to the sale of raw materials to GSK.

• Other operating expenses increased year-on-year due to a partial impairment of CureVac’s production facility.

While the production facility was initially planned and set up for commercial (large scale) production, CureVac no longer has large scale production obligations in addition to the strategic re-focus on technology innovation, research and development. Most parts of the production process can be scaled down to provide products for clinical production. Parts of the production process that cannot be scaled down were partially impaired in an amount of €36.6 million.

Financial Result (Finance Income and Expenses)

Net financial result for the three and nine months ended September 30, 2024, amounted to €2.2 million and €8.0 million, or a decrease of €3.1 million and €4.7 million, from €5.3 million and €12.7 million, respectively, for the same periods in 2023. This decrease was mainly driven by lower interest income on cash investments.

Pre-Tax Results

Pre-tax profit was €370.6 million and €229.4 million for the three and nine months ended September 30, 2024, compared to a pre-tax loss of €48.7 million and €173.5 million in the same periods of 2023.

Conference call and webcast details

CureVac will host a conference call and webcast today at 3 p.m. CET / 9 a.m. EST.
Dial-in numbers to participate in the conference call:

U.S. Toll-Free: +1-877-407-0989
International: +1-201-389-0921
Germany: 0800-182-0040 (landline access) / 0800-184-4713 (cell phone access)

The live webcast link can be accessed via the newsroom section of the CureVac website at View Source

Corresponding presentation slides will be posted shortly before the start of the webcast.

A replay will be made available at this website after the event.

On November 12, 2024 Crinetics Pharmaceuticals, Inc. (Nasdaq: CRNX) reported two abstracts from its transformative, in-house discovery and development programs will be presented at the upcoming North American Neuroendocrine Tumor Society Multidisciplinary NET Medical Symposium (NANETS 2024), taking place November 21-23, 2024, in Chicago (Press release, Crinetics Pharmaceuticals, NOV 12, 2024, View Source [SID1234648166]).

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"We are eager to share our latest pipeline progress at NANETS 2024. Crinetics is committed to the neuroendocrine tumor community, and we are now utilizing our world class drug discovery and development capabilities to support people living with both functional and non-functional NETs," said Scott Struthers, Ph.D., Founder and Chief Executive Officer of Crinetics. "We are excited to present preclinical data from our groundbreaking nonpeptide drug conjugate platform for our lead candidate CRN09682, an investigational anti-tumor therapy targeting SST2-expressing tumors, including NETs. We will also present data from the Phase 2 clinical study of our investigational drug candidate paltusotine, highlighting its ability to reduce the frequency and severity of carcinoid syndrome symptoms in patients with functional NETs."

CRN09682, is a first-in-class, somatostatin receptor 2 (SST2) targeted, nonpeptide drug conjugate (NDC). Built upon the well-validated concept of antibody-drug conjugates, Crinetics’ NDCs use a highly optimized small molecule G protein coupled receptor (GPCR) ligand, instead of an antibody, to deliver a potent anti-cancer agent to tumor cells with high selectivity and efficiency. CRN09682 was designed to provide enhanced tumor penetration, selectively bind to SST2 expressing tumor cells, induce internalization, and intracellularly release a potent anti-tumor agent, while minimizing systemic exposure and associated toxicities. In addition, CRN09682 is manufactured by traditional chemical synthesis methods, avoiding the complex and heterogeneous manufacturing methods required for antibody drug conjugates. Preclinical data to be presented at NANETS 2024 demonstrate the potent and selective anti-tumor activity of CRN09682, potentially providing a novel alternative for the treatment of NETs and other SST2-expressing tumors.

Another abstract will be featured as both an oral and poster presentation, which includes follow-up from an open-label Phase 2 carcinoid syndrome study of investigational candidate paltusotine, a once-daily, oral, nonpeptide, selective SST2 agonist being developed for the treatment of acromegaly and carcinoid syndrome. The NANETS presentation includes findings from all 36 trial participants, with new analyses that show paltusotine reduced the frequency and severity of carcinoid syndrome symptoms and was well tolerated, justifying further clinical development.

Data for paltusotine and CRN09682, along with additional information on NDCs will also be featured in a Crinetics-sponsored symposium titled "Paltusotine and CRN09682: Novel Nonpeptide Approaches to Treating Carcinoid Syndrome and Neuroendocrine Tumors" at the conference on Thursday, November 21, from 12:15-1:15 p.m. CT. Featured speakers include Scott Struthers and Dr. Aman Chauhan, leader of Neuroendocrine Oncology and Co-Leader Radiopharmaceutical Drug Development at Sylvester Comprehensive Cancer Center, University of Miami Health System.

Details on the abstracts to be presented at NANETS are shown below:

Title: A Novel Nonpeptide Drug Conjugate (NDC) for the Treatment of Somatostatin Receptor 2-Expressing Tumors
Date/Time: Poster: November 22 from 5:15 – 6:30 pm CT
Title: Once-daily Oral Paltusotine in the Treatment of Patients With Carcinoid Syndrome: Results From a Phase 2, Randomized, Parallel-Group Study
Date/Time: Oral: November 22 from 3:10 – 3:22 pm CT | Poster: November 22 from 5:15 – 6:30 pm CT

The poster presentations will be made available on the Crinetics website at the time of presentation in accordance with the NANETS embargo policy.

ABOUT CRN09682
CRN09682 is an investigational, potentially first-in-class, non-radioactive, nonpeptide drug conjugate (NDC) linking a somatostatin receptor 2 (SST2) agonist with the cytotoxic drug monomethyl auristatin E (MMAE) via a spacer and a cleavable linker for the treatment of neuroendocrine tumors (NETs) and potentially for use in other solid tumors that express SST2. The SST2 ligand on the NDC molecule binds to SST2 on the tumor cell surface and is internalized in the cell whereby enzymes cleave the MMAE and release it within the cell. MMAE is known to cause microtubule disruption leading to cell arrest and death. The NDC approach is intended to enhance tumor penetration, selectively bind to specific GPCR expressing tumor cells, induce internalization, and intracellularly release a potent anti-tumor agent, while minimizing systemic exposure and associated toxicities. Additionally, NDCs are manufactured by traditional chemical synthesis methods, avoiding the limitations of fermentation, bioconjugation, and heterogeneous manufacturing methods required by most ADCs. NETs are generally incurable when metastatic, regardless of tumor grade. Overall survival rates vary significantly by stage, grade, age at diagnosis, primary site, and time period of diagnosis.

ABOUT PALTUSOTINE
Crinetics’ lead development candidate, paltusotine, is the first investigational once-daily, oral, selective somatostatin receptor type 2 (SST2) nonpeptide agonist that has completed Phase 3 clinical development for acromegaly and is in Phase 2 clinical development for carcinoid syndrome associated with neuroendocrine tumors. It was designed by Crinetics with the goal of providing a once-daily, oral option for reliable and consistent control of acromegaly and carcinoid syndrome. In Phase 3 studies, once-daily, oral paltusotine maintained IGF-1 levels and symptom control in patients with acromegaly who were switched from monthly injectable medications (PATHFNDR-1) and rapidly decreased IGF-1 levels and symptom burden in medically untreated acromegaly patients (PATHFNDR-2). IGF-1 is the primary biomarker endocrinologists use to manage acromegaly patients. Results from the Phase 2 study in carcinoid syndrome provide supporting data and rationale for paltusotine to initiate a Phase 3 trial for another important indication related to the treatment of carcinoid syndrome in patients with neuroendocrine tumors.

On November 12, 2024 Corvus Pharmaceuticals, Inc. (Corvus or the Company) (Nasdaq: CRVS), a clinical-stage biopharmaceutical company, reported a business update and announced financial results for the third quarter ended September 30, 2024 (Press release, Corvus Pharmaceuticals, NOV 12, 2024, View Source [SID1234648165]).

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"There is strong interest from clinicians and patients in both of our clinical programs for soquelitinib – the registration Phase 3 clinical trial in PTCL and the Phase 1 clinical trial in atopic dermatitis – and we are pleased with ongoing enrollment in these trials," said Richard A. Miller, M.D., co-founder, president and chief executive officer of Corvus. "ITK inhibition offers a novel mechanism of action that inhibits multiple parallel signaling pathways that modulate T cell function and immunity, giving it broad potential across a range of indications in oncology and immune disease. Its clinical potential has already been demonstrated in PTCL and we look forward to presenting interim data from our Phase 1 clinical trial in atopic dermatitis in December. We are excited for the potential of ITK inhibition to provide a new oral treatment option for atopic dermatitis, with the potential for improved efficacy, and with a more convenient and tolerable profile than biologics."

Business Update and Strategy

Prioritized Program: Soquelitinib (Corvus’ selective ITK inhibitor)

Soquelitinib for Immune Diseases

Corvus continues to enroll patients at multiple clinical sites in its randomized, placebo-controlled Phase 1 clinical trial of soquelitinib in patients with moderate to severe atopic dermatitis. The trial is planned to enroll 64 patients that have failed at least one prior therapy across four different 28-day dosing regimens of soquelitinib compared to a placebo group. Patients are followed for an additional 30 days after completing the 28 day course of therapy. The endpoints include safety and improvement in the Eczema Area and Severity Index. Patients and physicians are blinded to the treatment assignment. Enrollment in the first cohort (100 mg, twice per day) has been completed and the data review committee has met and found no safety signals. The second cohort (200 mg, once-daily) is now enrolling patients.
Corvus plans to announce interim data from the Phase 1 clinical trial in December 2024.
In November, Corvus plans to present new preclinical data highlighting the potential of soquelitinib to prevent lung damage, inflammation and pulmonary hypertension caused by systemic sclerosis at ACR Convergence 2024, the annual meeting of the American College of Rheumatology.
Corvus continues to advance its next-generation ITK inhibitor preclinical product candidates, which were designed to deliver precise T-cell modulation that is optimized for specific immunology indications.
Soquelitinib for T Cell Lymphoma

Corvus continues to enroll patients in a registrational Phase 3 clinical trial of soquelitinib in patients with relapsed PTCL at multiple sites. This randomized controlled trial is anticipated to enroll a total of 150 patients with relapsed PTCL and is evaluating soquelitinib versus physicians’ choice of either belinostat or pralatrexate. The primary endpoint of the trial is progression free survival.
There are no FDA fully approved agents for the treatment of relapsed PTCL and the FDA has granted soquelitinib Orphan Drug Designation for the treatment of T cell lymphoma and Fast Track designation for treatment of adult patients with relapsed or refractory peripheral T cell lymphoma after at least 2 lines of systemic therapy.
Collaboration with Kidney Cancer Research Consortium: Ciforadenant (adenosine A2a receptor inhibitor)

Corvus is collaborating with the Kidney Cancer Research Consortium in a Phase 1b/2 clinical trial evaluating ciforadenant as a potential first line therapy for metastatic renal cell cancer (RCC) in combination with ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1). The efficacy endpoint for the trial is deep response rate, defined as CR plus PRs of greater than 50% tumor volume reduction. The clinical trial is expected to enroll up to 60 patients and as of September 30, 2024, a total of 46 patients were enrolled in the trial. The protocol defined, interim pre-specified statistical threshold for efficacy is a 50% increase above the 32% deep response rate seen with previous ipilimumab/nivolumab combination trials in RCC conducted by investigators at the Kidney Cancer Research Consortium. The analysis of the clinical trial continues to meet the threshold for efficacy and therefore enrollment continues. Along with our partners at the Kidney Cancer Research Consortium, we have decided to continue our follow-up of patients on the trial before presenting the data. Therefore, we will not be presenting this data at the GU Malignancy conference taking place in late November and will instead target a presentation sometime in 2025.
The Phase 1b/2 clinical trial in patients with metastatic RCC is supported by data presented in November at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 39th Annual Meeting highlighting the potential of ciforadenant to overcome immunotherapy resistance in metastatic castration resistant prostate cancer.
Financial Results

As of September 30, 2024, Corvus had cash, cash equivalents and marketable securities of $41.7 million as compared to $27.1 million as of December 31, 2023. In October 2024, a holder of 1,677,220 common stock warrants early exercised all of their warrants resulting in cash proceeds of approximately $5.9 million. Corvus expects full year 2024 net cash used in operating activities to be between approximately $25 million and $26 million, resulting in a projected cash balance of between approximately $38 million and $39 million at December 31, 2024. Based on its current plans, Corvus expects its cash to fund operations into 2026.

Research and development expenses for the three months ended September 30, 2024 totaled $5.2 million compared to $4.0 million for the same period in 2023. The increase of approximately $1.2 million was primarily due to higher clinical trial costs associated with the development of soquelitinib.

The net loss for the three months ended September 30, 2024 was $40.2 million compared to a net loss of $6.0 million for the same period in 2023. Total stock compensation expense for the three months ended September 30, 2024 was $0.7 million compared to $0.5 million for the same period in 2023 and the non-cash loss from Corvus’ equity method investment in Angel Pharmaceuticals was $0.7 million for the three months ended September 30, 2024 compared to a loss of $0.9 million for the same period in 2023. In addition, the Company recorded a non-cash loss of $32.8 million related to an increase in the fair value of its warrant liability during the three months ended September 30, 2024 due an increase in the Company’s stock price from $1.82 at June 30, 2024 to $5.28 at September 30, 2024. The Company issued approximately 17.1 million common stock warrants in its May 2024 registered direct offering with an exercise price of $3.50 per common stock warrant. After the October 2024 early exercise of 1,677,220 common stock warrants, approximately 15.4 million common stock warrants remain outstanding. The common stock warrants expire on June 30, 2025.

Conference Call Details
Corvus will host a conference call and webcast today, Tuesday, November 12, 2024, at 4:30 p.m. ET (1:30 p.m. PT), during which time management will provide a business update and discuss the third quarter 2024 financial results. The conference call can be accessed by dialing 1- 800-717-1738 (toll-free domestic) or 1- 646-307-1865 (international) or by clicking on this link for instant telephone access to the event. The live webcast may be accessed via the investor relations section of the Corvus website. A replay of the webcast will be available on Corvus’ website for 90 days.