On February 22 2024 Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading clinical-stage gene editing company focused on revolutionizing medicine with CRISPR-based therapies, reported operational highlights and financial results for the fourth quarter and year ended December 31, 2023 (Press release, Intellia, FEB 22, 2024, View Source [SID1234640389]).

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"We’re off to a very strong start in 2024 as we execute against our strategic priorities to realize the full potential of CRISPR-based gene editing," said Intellia President and Chief Executive Officer John Leonard, M.D. "We are focused on rapidly enrolling patients in the pivotal Phase 3 MAGNITUDE trial of NTLA-2001 for the treatment of ATTR amyloidosis with cardiomyopathy and expect to dose the first patient in the first quarter of this year. We also remain on track to begin the Phase 3 trial for our second in vivo CRISPR-based therapy, NTLA-2002 for hereditary angioedema, later in the year. At the same time, we continue to expand both the technical approaches for CRISPR-based therapies, as well as the range of diseases they can potentially address. We plan to initiate two first-in-human studies for product candidates leveraging our modular gene insertion platform to produce a deficient protein – one wholly owned program focused on alpha-1 antitrypsin deficiency-associated lung disease and, together with Regeneron, a second program focused on hemophilia B. Finally, we are progressing our editing capabilities, including DNA writing, and applying them to diseases that originate outside of the liver. We announced last week a new collaboration with ReCode Therapeutics to advance novel gene editing treatments directly to the lung in patients with cystic fibrosis. These pipeline and platform efforts move us closer to setting a new standard of care for people living with serious diseases and expanding Intellia’s impact as the leading gene editing company."

Fourth Quarter 2023 and Recent Operational Highlights

Transthyretin (ATTR) Amyloidosis

NTLA-2001: NTLA-2001 is an investigational in vivo CRISPR-based therapy designed to inactivate the TTR gene in the liver and thereby prevent the production of transthyretin (TTR) protein for the treatment of ATTR amyloidosis. NTLA-2001 offers the possibility of halting and reversing the disease by driving a deep, consistent and potentially lifelong reduction in TTR protein after a single dose. Intellia leads development and commercialization of NTLA-2001 in collaboration with Regeneron.
ATTR Amyloidosis with Cardiomyopathy (ATTR-CM):
Intellia is actively enrolling patients, including in the U.S., in the pivotal Phase 3 MAGNITUDE trial. The Company is on track to dose the first patient in Q1 2024 and continues to open new clinical sites.
Hereditary ATTR Amyloidosis with Polyneuropathy (ATTRv-PN):
Intellia is actively preparing for a global pivotal Phase 3 study of NTLA-2001 for the treatment of ATTRv-PN.
The Company plans to present updated data from the ongoing Phase 1 study in 2024.
Hereditary Angioedema (HAE)

NTLA-2002: NTLA-2002 is a wholly owned, investigational in vivo CRISPR-based therapy designed to knock out the KLKB1 gene in the liver, with the goal of lifelong control of HAE attacks after a single dose.
Intellia plans to initiate the global pivotal Phase 3 study, including U.S. patients, in the second half of 2024, subject to regulatory feedback.
As previously announced in January, Intellia completed enrollment and dosing in the Phase 2 portion of the Phase 1/2 study in adults with HAE. The Company plans to present updated data from the Phase 1 and new data from the Phase 2 portion in 2024.
In January, the Company announced that positive interim results from the Phase 1 portion of the Phase 1/2 study of NTLA-2002 were published in the New England Journal of Medicine (NEJM). The reported data showed that a single dose of NTLA-2002 led to a 95% mean reduction in monthly HAE attack rate across all 10 patients in the Phase 1 portion. NTLA-2002 was well tolerated at all dose levels. The most frequent adverse events reported were mild, transient infusion-related reactions and fatigue.
During the fourth quarter of 2023, Intellia received Priority Medicines (PRIME) designation from the European Medicines Agency and orphan drug designation from the European Commission for NTLA-2002.
In Vivo Targeted Gene Insertion

NTLA-3001 for Alpha-1 Antitrypsin Deficiency (AATD)-Associated Lung Disease: NTLA-3001 is a wholly owned, first-in-class CRISPR-mediated in vivo targeted gene insertion development candidate for the treatment of AATD-associated lung disease. It is designed to precisely insert a healthy copy of the SERPINA1 gene, which encodes the alpha-1 antitrypsin (A1AT) protein, with the potential to restore permanent expression of functional A1AT protein to therapeutic levels after a single dose.
In December 2023, Intellia submitted a Clinical Trial Application (CTA) to initiate a first-in-human, Phase 1 study of NTLA-3001. The Company plans to dose the first patient in 2024.
Hemophilia B: In February, Regeneron and Intellia announced the clearance by the U.S. Food and Drug Administration of its investigational new drug application to initiate a clinical trial of its investigational in vivo CRISPR-based Factor 9 gene insertion program for people living with hemophilia B. A Phase 1, first-in-human study is expected to begin in mid-2024. Regeneron leads development and commercialization of hemophilia A and B programs in collaboration with Intellia.
In Vivo Platform Expansion Including to Tissues Outside of the Liver

In February, Intellia and ReCode announced a strategic collaboration to develop novel genomic medicines for the treatment of cystic fibrosis (CF). The collaboration will leverage Intellia’s proprietary CRISPR-based gene editing platform, including its DNA writing technology, and ReCode’s proprietary Selective Organ Targeting (SORT) lipid nanoparticle delivery platform to precisely correct one or more CF disease-causing gene mutations.
In October 2023, Intellia and Regeneron announced an expanded research collaboration to develop additional in vivo CRISPR-based gene editing therapies focused on neurological and muscular diseases.
In October 2023, Regeneron exercised its option to extend the existing technology collaboration term with Intellia for two years. The technology collaboration term now extends to April 2026, and Intellia will receive a $30 million payment due in April 2024.
Ex Vivo Program Updates

Intellia is advancing multiple preclinical programs, wholly owned and in collaboration with partners, utilizing its allogeneic platform for the treatment of immuno-oncology and autoimmune diseases. The Company’s proprietary allogeneic cell engineering platform is designed to avoid both T cell- and NK cell-mediated rejection, a key unsolved challenge with other investigational allogeneic approaches.
Upcoming Events

The Company will participate in the following events in March:

TD Cowen 44th Annual Health Care Conference, March 4, Boston
Leerink Global Biopharma Conference, March 12, Miami
Barclays Global Healthcare Conference, March 13, Miami
Fourth Quarter and Full-Year 2023 Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $1.0 billion as of December 31, 2023, compared to $1.3 billion as of December 31, 2022. The decrease was driven by cash used to fund operations of $448.8 million. The decrease was offset in part by $119.8 million of net equity proceeds from the Company’s "At the Market" (ATM) program, $49.8 million of interest income, $18.7 million of reimbursement from its collaborators, and $10.5 million in proceeds from employee-based stock plans. The cash position is expected to fund operations into mid-2026.
Collaboration Revenue: Collaboration revenue decreased by $15.5 million to negative $1.9 million during the fourth quarter of 2023, compared to $13.6 million during the fourth quarter of 2022. This decrease was mainly driven by a $10.3 million one-time revenue recognition adjustment related to Regeneron extending the technology collaboration to April 2026. Intellia will receive a $30.0 million payment due in April 2024 as part of the Regeneron extension.
R&D Expenses: Research and development expenses increased by $9.0 million to $109.0 million during the fourth quarter of 2023, compared to $100.0 million during the fourth quarter of 2022. This increase was primarily driven by the advancement of our lead programs and personnel growth to support these programs. Stock-based compensation expense included in research and development expenses was $21.7 million for the fourth quarter of 2023.
G&A Expenses: General and administrative expenses increased by $5.4 million to $29.0 million during the fourth quarter of 2023, compared to $23.6 million during the fourth quarter of 2022. This increase was primarily related to an increase in stock-based compensation of $4.3 million. Stock-based compensation expense included in general and administrative expenses was $13.3 million for the fourth quarter of 2023.
Net Loss: The Company’s net loss was $132.2 million for the fourth quarter of 2023, compared to $113.4 million during the fourth quarter of 2022.
Conference Call to Discuss Fourth Quarter and Full-Year 2023 Results

The Company will discuss these results on a conference call today, Thursday, February 22, at 8 a.m. ET.
To join the call:

U.S. callers should dial 1-833-316-0545 and international callers should dial 1-412-317-5726 approximately five minutes before the call. All participants should ask to be connected to the Intellia Therapeutics conference call.
Please visit this link for a simultaneous live webcast of the call.
A replay of the call will be available through the Events and Presentations page of the Investors & Media section on Intellia’s website at intelliatx.com, beginning on February 22, at 12 p.m. ET.

On February 22, 2024 Immunocore Holdings plc (Nasdaq: IMCR) ("Immunocore" or the "Company"), a commercial-stage biotechnology company pioneering and delivering transformative immunomodulating medicines to radically improve outcomes for patients with cancer, infectious diseases and autoimmune diseases, reported that it has entered into a clinical trial collaboration and supply agreement with Bristol Myers Squibb (NYSE:BMY) to investigate Immunocore’s ImmTAC bispecific TCR (T cell receptor) candidate targeting PRAME HLA-A02, IMC-F106C, in combination with Bristol Myers Squibb’s nivolumab, in first-line advanced cutaneous melanoma (Press release, Immunocore, FEB 22, 2024, View Source [SID1234640388]).

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Under the terms of the collaboration, Immunocore will sponsor and fund the registrational Phase 3 clinical trial of IMC-F106C in combination with nivolumab in first-line advanced cutaneous melanoma (PRISM-MEL-301), and Bristol Myers Squibb will provide nivolumab.

The PRISM-MEL-301 trial will randomize HLA-A*02:01+ first-line advanced cutaneous melanoma patients to IMC-F106C + nivolumab versus a control arm of either nivolumab or the fixed-dose combination of nivolumab and relatlimab, depending on the country where the patient is enrolled. Immunocore plans to randomize the first patient in this trial in the first quarter of 2024.

About PRISM-MEL301 – Phase 3 trial with IMC-F106C (PRAME HLA-A02) in 1L advanced cutaneous melanoma

The Phase 3 registrational trial (NCT06112314) will randomize patients with previously untreated, HLA-A*02:01 positive, advanced melanoma to IMC-F106C + nivolumab versus nivolumab or the fixed-dose combination of nivolumab and relatlimab, depending on the country where the patient is enrolled. The trial will initially randomize to three arms: two IMC-F106C dose regimens (40 mcg and 160 mcg) and control arm and will discontinue one of the F106C dose regimens after an initial review of the first 60 patients randomized to the two experimental arms (90 patients randomized total). The primary endpoint of the trial is progression free survival (PFS) by blinded independent central review (BICR), with secondary endpoints of overall survival (OS) and overall response rate (ORR), as well as safety.

On February 22, 2024 Guardant Health, Inc. (Nasdaq: GH), a leading precision oncology company, reported financial results for the quarter and full year ended December 31, 2023 (Press release, Guardant Health, FEB 22, 2024, View Source [SID1234640387]).

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Fourth Quarter 2023 Financial Highlights
•Revenue of $155.1 million for the fourth quarter of 2023, an increase of 22% over the fourth quarter of 2022
•Reported 46,400 tests to clinical customers and 9,500 tests to biopharmaceutical customers in the fourth quarter of 2023, representing increases of 29% and 16%, respectively, over the fourth quarter of 2022
Full Year 2023 Financial Highlights
•Revenue of $563.9 million for the full year 2023, an increase of 25% over the full year 2022
•Reported 172,900 tests to clinical customers and 29,900 tests to biopharmaceutical customers in the full year 2023, representing an increase of 39% and 15%, respectively, over the full year 2022
•Lowered full year 2023 operating expenses and improved free cash flow compared to full year 2022
•Ended the year with $1.2 billion in cash, cash equivalents and marketable debt securities
Recent Operating Highlights
•Improved ASPs with Guardant360 LDT CMS reimbursement increased from $3,500 to $5,000 effective January 1, 2024
•Published first paper for Shield demonstrating improved adherence with blood-based CRC screening
•Collaborated with US Oncology Network and leading community oncology practices to increase the use of biomarker testing to identify patients who would benefit from therapies
•Appointed Terilyn Juarez Monroe as chief people officer
"2023 marked another strong year for Guardant. This was underscored by our team’s exceptional execution to deliver strong clinical volumes, which grew nearly 40%," said Helmy Eltoukhy, co-founder and co-CEO. "We also surpassed an important milestone by achieving cash flow breakeven in our Therapy Selection business by year-end. Looking ahead to 2024, we are well positioned for continued growth across our oncology product portfolio and have a strong foundation to deliver long-term shareholder value."
"We are continuing to make steady progress with FDA on our PMA submission for Shield and look forward to the upcoming Advisory Committee Panel as the next phase of the review process," said AmirAli Talasaz, co-founder and co-CEO. "2024 will be a pivotal year for our screening business as we prepare to launch our Shield IVD test following expected FDA approval. We are excited to see the impact our test will have to CRC screening when it is broadly launched later this year."
Fourth Quarter 2023 Financial Results
Revenue was $155.1 million for the fourth quarter of 2023, a 22% increase from $126.9 million for the corresponding prior year period. Precision oncology revenue grew 25%, to $142.2 million for the fourth quarter of 2023, from $113.8 million for the corresponding prior year period, driven predominantly by an increase in clinical and biopharma testing volume, which grew 29% and 16%, respectively, over the prior year period. Development services and other revenue was $12.9 million for the fourth quarter of 2023, compared to $13.1 million for the corresponding prior year period.
Gross profit, or total revenue less cost of precision oncology testing and cost of development services and other, was $92.5 million for the fourth quarter of 2023, an increase of $12.8 million from $79.8 million for the corresponding prior year period. Gross margin, or gross profit divided by total revenue, was 60%, as compared to 63% for the corresponding prior year period. Precision oncology gross margin was 60% in the fourth quarter of 2023, as compared to 62% in the prior year period. The reduction is primarily due to changes in product mix. Development services and other gross margin was 60% in the fourth quarter of 2023, as compared to 74% in the prior year period. The change is primarily due to the cost of processing an increased volume of Shield LDT tests, for which we are currently booking minimal revenue.

Operating expenses (research and development expense, sales and marketing expense, and general and administrative expense) were $206.6 million for the fourth quarter of 2023, as compared to $225.9 million for the corresponding prior year period. Other operating expense was $83.4 million for the fourth quarter of 2023, related to a non-recurring legal accrual. No such other operating expense was recorded for the corresponding prior year period. Non-GAAP operating expenses were $183.1 million for the fourth quarter of 2023, as compared to $201.2 million for the corresponding prior year period.
Net loss was $187.0 million for the fourth quarter of 2023, as compared to $139.9 million for the corresponding prior year period. Net loss per share was $1.58 for the fourth quarter of 2023, as compared to $1.36 for the corresponding prior year period. The year-over-year increase in net loss is primarily due to the non-recurring $83.4 million legal accrual, partially offset by a $32.0 million year over year improvement in loss from operations, excluding the legal accrual impact, and a $11.7 million increase in interest income.
Non-GAAP net loss was $75.9 million for the fourth quarter of 2023, as compared to $119.6 million for the corresponding prior year period. Non-GAAP net loss per share was $0.64 for the fourth quarter of 2023, as compared to $1.17 for the corresponding prior year period.
Adjusted EBITDA loss was $78.4 million for the fourth quarter of 2023, as compared to a $109.8 million loss for the corresponding prior year period.
Free cash flow for the fourth quarter of 2023 was negative $82.8 million, as compared to negative $100.8 million for the corresponding prior year period. Cash, cash equivalents and marketable debt securities were $1.2 billion as of December 31, 2023.

Full Year 2023 Financial Results

Revenue was $563.9 million for 2023, a 25% increase from $449.5 million for the corresponding prior year period. Precision oncology revenue grew 31%, to $514.2 million for 2023, from $392.0 million for the corresponding prior year period, driven predominantly by an increase in clinical and biopharma testing volume, which grew 39% and 15%, respectively, over the prior year period. Development services and other revenue decreased by 14%, to $49.7 million for 2023, from $57.5 million for the corresponding prior year period, primarily due to the timing and amount of milestones related to our companion diagnostics collaboration projects and other service agreements with biopharmaceutical customers, and a reduction in royalty revenue.

Gross profit, or total revenue less cost of precision oncology testing and cost of development services and other, was $336.9 million for 2023, an increase of $43.7 million from $293.2 million for the corresponding prior year period. Gross margin, or gross profit divided by total revenue, was 60%, as compared to 65% for the corresponding prior year period. Precision oncology gross margin was 60% in the year of 2023, as compared to 62% in the prior year period. The reduction is primarily due to changes in product mix. Development services and other gross margin was 57% in the year of 2023, as compared to 86% in the prior year period. The change is primarily due to the inclusion of the full year 2023 cost of processing Shield LDT samples as part of our screening market development activities, for which we are currently booking minimal revenue, compared to the inclusion of the fourth quarter only cost in 2022.
Operating expenses (research and development expense, sales and marketing expense, and general and administrative expense) were $818.2 million for 2023, as compared to $837.6 million for the corresponding prior year period. Other operating expense was $83.4 million for 2023, related to the non-recurring legal accrual discussed above. No such other operating expense was recorded for the corresponding prior year period. Non-GAAP operating expenses were $729.2 million for 2023, as compared to $736.6 million for the corresponding prior year period.
Net loss was $479.4 million for 2023, as compared to $654.6 million for the corresponding prior year period. Net loss per share was $4.28 for 2023, as compared to $6.41 for the corresponding prior year period. The year-over-year improvement in net loss is primarily due to a $99.8 million fair value adjustment related to the Joint Venture acquisition recorded in 2022, a $87.5 million positive change in unrealized gains and losses, a $63.1 million year over year improvement in loss from operations, excluding the legal accrual impact, and a $29.3 million increase in interest income, partially offset by the $83.4 million legal accrual discussed above, and a $23.8 million increase in impairment on non-marketable equity securities.
Non-GAAP net loss was $352.3 million for 2023, as compared to $435.4 million for the corresponding prior year period. Non-GAAP net loss per share was $3.15 for 2023, as compared to $4.26 for the corresponding prior year period.
Adjusted EBITDA loss was $344.2 million for 2023, as compared to a $403.4 million loss for the corresponding prior year period.
Free cash flow for 2023 was negative $345.5 million, as compared to negative $386.9 million for the corresponding prior year period.

2024 Guidance
Guardant Health expects full year 2024 revenue excluding screening to be in the range of $655 to $670 million, representing growth of 16% to 19% compared to full year 2023, and full year 2024 non-GAAP gross margin excluding screening to be in the range of 60% to 62%. Guardant Health expects total non-GAAP operating expenses to be in the range of $740 to $750 million, representing a 1% to 3% increase compared to full year 2023, and free cash flow to be in the range of negative $320 to $330 million in 2024, an improvement compared to the full year 2023.
Webcast Information
Guardant Health will host a conference call to discuss the fourth quarter and full year 2023 financial results after market close on Thursday, February 22, 2024 at 1:30 pm Pacific Time / 4:30 pm Eastern Time. A webcast of the conference call can be accessed at View Source The webcast will be archived and available for replay for at least 90 days after the event.
Non-GAAP Measures
Guardant Health has presented in this release certain financial information in accordance with U.S. Generally Accepted Accounting Principles (GAAP) and also on a non-GAAP basis, including non-GAAP cost of precision oncology testing, non-GAAP cost of development services and other, non-GAAP cost of screening, non-GAAP gross profit, non-GAAP gross profit excluding cost of screening, non-GAAP research and development expense, non-GAAP sales and marketing expense, non-GAAP general and administrative expense, non-GAAP other operating expense, non-GAAP loss from operations, non-GAAP net loss, non-GAAP net loss per share, basic and diluted, adjusted EBITDA, and free cash flow.

We define our non-GAAP measures as the applicable GAAP measure adjusted for the impacts of stock-based compensation and related employer payroll tax payments, contingent consideration, amortization of intangible assets, fair value adjustments on marketable equity securities, impairment of non-marketable equity securities and other related assets, fair value adjustments of noncontrolling interest liability, and other non-recurring items.
Adjusted EBITDA is defined as net loss adjusted for interest income; interest expense; other income (expense), net; provision for (benefit from) income taxes; depreciation and amortization expense; stock-based compensation expense and related employer payroll tax payments; contingent consideration; fair value adjustments of noncontrolling interest liability; and other non-recurring items. Free cash flow is defined as net cash used in operating activities in the period less purchase of property and equipment in the period.

We believe that the exclusion of certain income and expenses in calculating these non-GAAP financial measures can provide a useful measure for investors when comparing our period-to-period core operating results, and when comparing those same results to that published by our peers. We exclude certain items because we believe that these income and expenses do not reflect expected future operating performance. Additionally, certain items are inconsistent in amounts and frequency, making it difficult to perform a meaningful evaluation of our current or past operating performance. We use these non-GAAP financial measures to evaluate ongoing operations, for internal planning and forecasting purposes, and to manage our business.

These non-GAAP financial measures are not intended to be considered in isolation from, as substitute for, or as superior to, the corresponding financial measures prepared in accordance with GAAP. There are limitations inherent in non-GAAP financial measures because they exclude charges and credits that are required to be included in a GAAP presentation, and do not present the full measure of our recorded costs against its revenue. In addition, our definition of the non-GAAP financial measures may differ from non-GAAP measures used by other companies.

On February 22, 2024 Elevation Oncology, Inc. (Nasdaq: ELEV), an innovative oncology company focused on the discovery and development of selective cancer therapies to treat patients across a range of solid tumors with significant unmet medical needs, reported that it has expanded its ongoing Phase 1 clinical trial of EO-3021 outside the United States, dosing the first patient in Japan (Press release, Elevation Oncology, FEB 22, 2024, View Source;utm_medium=rss&utm_campaign=elevation-oncology-expands-ongoing-phase-1-clinical-trial-of-eo-3021-globally-dosing-first-patient-in-japan [SID1234640386]). This trial is evaluating the safety, tolerability and preliminary anti-tumor activity of EO-3021 in patients with advanced, unresectable or metastatic solid tumors likely to express Claudin 18.2, including gastric, gastroesophageal junction, pancreatic or esophageal cancers.

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"We are pleased to expand our clinical development efforts outside of the United States and into Japan where there is a large number of patients with gastric cancer who could benefit from EO-3021," said Valerie Malyvanh Jansen, M.D., Ph.D., Chief Medical Officer of Elevation Oncology. "Claudin 18.2 is expressed in most gastric adenocarcinomas and is increasingly recognized as an important therapeutic target, which can be effectively addressed with an antibody drug conjugate (ADC). We are excited to have dosed our first patient in Japan, as we continue to execute on our mission of delivering novel, selective cancer therapies that can offer better outcomes to patients."

"Despite recent advancements in the treatment of gastric cancer and improvements in mortality, there remains a significant need for new treatment options that offer patients improved outcomes," said Kohei Shitara, M.D., Chief, Department of Gastrointestinal Oncology, National Cancer Center Hospital East in Kashiwa, Japan and principal investigator on the Phase 1 clinical trial, "Based on preclinical and early clinical data, I believe EO-3021 has the potential to overcome the limitations of other therapeutic modalities to deliver benefit to patients with varying levels of Claudin 18.2 expression. I am excited to dose patients with EO-3021 and to have access to this much-needed option for patients in Japan."

Elevation Oncology’s Phase 1 clinical trial (NCT05980416) is an open-label, multi-center dose escalation and expansion study to evaluate the safety, tolerability and preliminary anti-tumor activity of EO-3021. An additional objective of the study will be to assess the association of Claudin 18.2 expression and objective response. The study is recruiting patients with advanced unresectable or metastatic solid tumors likely to express Claudin 18.2, including gastric, gastroesophageal junction, pancreatic or esophageal cancers, at multiple sites in the United States and Japan. Elevation Oncology expects to provide an update from the trial in mid-2024, with additional data expected in the first half of 2025.

About EO-3021

EO-3021 (also known as SYSA1801) is a differentiated, clinical-stage antibody drug conjugate (ADC) with best-in-class potential comprised of an immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that targets Claudin 18.2. EO-3021 is site-specifically conjugated to the monomethyl auristatin E (MMAE) payload via a cleavable linker with a drug-to-antibody ratio (DAR) of 2. Claudin 18.2 is a specific isoform of Claudin 18 that is normally expressed in gastric epithelial cells. During malignant transformation, the tight junctions may become disrupted, exposing Claudin 18.2 and allowing them to be accessible by Claudin 18.2 targeting agents. Elevation Oncology is evaluating EO-3021 in a Phase 1 study (NCT05980416) in patients with advanced, unresectable or metastatic solid tumors likely to express Claudin 18.2 including gastric, gastroesophageal junction, pancreatic or esophageal cancers.

Elevation Oncology has the exclusive rights to develop and commercialize EO-3021 in all global territories outside Greater China.

On February 22, 2024 Dynavax Technologies Corporation (Nasdaq: DVAX), a commercial-stage biopharmaceutical company developing and commercializing innovative vaccines, reported financial results for the fourth quarter and full year ended December 31, 2023 (Press release, Dynavax Technologies, FEB 22, 2024, View Source [SID1234640385]).

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"2023 was characterized by record revenue growth for HEPLISAV-B, and the achievement of becoming the market share leader in the two largest growth segments, demonstrating important progress toward our goal of establishing HEPLISAV-B as the leading vaccine in the U.S. adult hepatitis B vaccine market," said Ryan Spencer, Chief Executive Officer of Dynavax. "We expect 2024 to be an important year in building a vaccine portfolio of best-in-class products, including further growing the HEPLISAV-B brand as well as advancing our pipeline programs into clinical trial initiations and data readouts. Importantly, our strong financial position provides us with the optionality to continue to build value across our business, including through investing to drive the HEPLISAV-B market opportunity, advancing and expanding our R&D efforts, and pursuing strategic opportunities to accelerate our growth."

BUSINESS UPDATES

HEPLISAV-B [Hepatitis B Vaccine (Recombinant), Adjuvanted]

HEPLISAV-B vaccine is the first and only adult hepatitis B vaccine approved in the U.S., the European Union and Great Britain that enables series completion with only two doses in one month. Hepatitis B vaccination is universally recommended for adults aged 19-59 in the U.S.

HEPLISAV-B vaccine net product revenue for the fourth quarter and full year 2023 were approximately $51.1 million and $213.3 million, respectively, representing year-over-year growth of approximately 46% and 69% compared to the fourth quarter and full year 2022.
HEPLISAV-B total market share in the U.S. increased to approximately 42% at the end of 2023, compared to approximately 35% at the end of 2022.
HEPLISAV-B market share in the retail pharmacy segment increased to approximately 58% at the end of 2023, compared to approximately 42% at the end of 2022. HEPLISAV-B market share in the Integrated Delivery Networks (IDNs) and Large Clinics segment increased to approximately 56% at the end of 2023, compared to approximately 47% at the end of 2022.
A supplemental Biologic License Application (sBLA) for HEPLISAV-B vaccination of adults on hemodialysis is currently under review by the U.S. Food and Drug Administration (FDA) with a Prescription Drug User Fee Act (PDUFA) action date planned for May 13, 2024.
Driven by the Centers for Disease Control and Prevention’s Advisory Committee of Immunization Practices (ACIP) universal recommendation for adult hepatitis B vaccination, the hepatitis B vaccine market continues to expand in the U.S. and Dynavax believes the U.S. market has the potential to grow to approximately $800 million by 2027, with HEPLISAV-B well-positioned to achieve a majority market share.
Clinical Pipeline

Dynavax is advancing a pipeline of differentiated product candidates that leverage its CpG 1018 adjuvant, which has demonstrated its ability to enhance the immune response with a favorable tolerability profile in a wide range of clinical trials and real-world commercial use.

Shingles vaccine program:

Z-1018 is an investigational vaccine candidate being developed for the prevention of shingles in adults aged 50 and older.

Dynavax recently submitted an Investigational New Drug Application (IND) to the U.S. FDA to support initiation of a Phase 1/2 trial of Z-1018 in the first half of 2024.
Tdap vaccine program:

Tdap-1018 is an investigational vaccine candidate intended for active booster immunization against tetanus, diphtheria, and pertussis (Tdap).

Dynavax plans to submit an IND to the U.S. FDA to support the initiation of a Phase 2 human challenge study of Tdap-1018 in the second half of 2024, upon completion of the independent study conducted by the Canadian Center for Vaccinology to establish the human challenge dose.
Plague vaccine program:

Dynavax is developing a plague (rF1V) vaccine candidate adjuvanted with CpG 1018 currently in a Phase 2 clinical trial in collaboration with, and fully funded by, the U.S. Department of Defense.

Dynavax anticipates top line data for the randomized, active-controlled Phase 2 clinical trial evaluating immunogenicity, safety, and tolerability of the plague vaccine candidate in 2024.
FOURTH QUARTER AND FULL YEAR 2023 FINANCIAL HIGHLIGHTS

Total Revenues and Net Product Revenue.

HEPLISAV-B vaccine net product revenue was $51.1 million for the fourth quarter of 2023, compared to $34.9 million for the fourth quarter of 2022, and $213.3 million for the full year 2023, compared to $125.9 million for the full year 2022.
Other revenue was $4.5 million for the fourth quarter of 2023, compared to $2.3 million for the fourth quarter of 2022, and $19.0 million for the full year 2023, compared to $9.0 million for the full year 2022. Other revenue primarily includes revenue from the plague vaccine agreement with the U.S. Department of Defense. The increase was primarily driven by the advancement into a nonhuman primate challenge study.
No CpG 1018 adjuvant product revenue was recorded in the fourth quarter and full year 2023, compared to $147.2 million and $587.7 million in the same periods of 2022, respectively, due to completion of all obligations and product delivery under the Company’s CpG 1018 adjuvant COVID-19 collaboration agreements as of the end of 2022.
Total revenues for the fourth quarter of 2023 were $55.6 million, compared to $184.5 million for the fourth quarter of 2022, and $232.3 million for the full year 2023, compared to $722.7 million for the full year 2022.
Cost of Sales – Product. Cost of sales – product for HEPLISAV-B the fourth quarter of 2023 decreased to $8.7 million, compared to $12.4 million for the fourth quarter of 2022, and $50.2 million for the full year 2023, compared to $40.1 million for the full year 2022.

Research and Development Expenses (R&D). R&D expenses for the fourth quarter of 2023 increased to $14.1 million, compared to $12.9 million for the fourth quarter of 2022, and $54.9 million for the full year 2023, compared to $46.6 million for the full year 2022. The increase was primarily driven by continued investments in advancing our clinical and preclinical development programs and collaborations.

Selling, General, and Administrative Expenses (SG&A). SG&A expenses for the fourth quarter of 2023 increased to $41.3 million, compared to $31.0 million for the fourth quarter of 2022, and $152.9 million for the full year 2023, compared to $131.4 million for the full year 2022. The increase was primarily driven by higher compensation and related personnel costs and an overall increase in targeted commercial and marketing efforts designed to increase HEPLISAV-B market share and maximize the opportunities presented by the ACIP’s universal recommendation.

Net Income. GAAP net income was $0.2 million, or less than $0.01 per share (basic and diluted) in the fourth quarter of 2023, compared to GAAP net income of $67.7 million, or $0.53 per share (basic) and $0.45 per share (diluted) in the fourth quarter of 2022. GAAP net loss was $6.4 million, or $0.05 per share (basic and diluted) for the full year 2023, compared to GAAP net income of $293.2 million, or $2.32 per share (basic) and $1.97 per share (diluted) for the full year 2022.

Cash and Marketable Securities. Cash, cash equivalents and marketable securities were $742.3 million as of December 31, 2023.

2024 FINANCIAL GUIDANCE

Dynavax is providing the following full year 2024 financial guidance, based on the Company’s current operating plan:

HEPLISAV-B net product revenue between approximately $265 – $280 million, including approximately $3 million in ex-U.S. sales through commercialization agreement with Bavarian Nordic in Germany
HEPLISAV-B gross margin of approximately 80% for full year 2024
Research and development expenses between approximately $60 – $75 million
Selling, general and administrative expenses between approximately $160 – $180 million
Expect to be cash flow positive for full year ended December 31, 2024
Conference Call and Webcast Information

Dynavax will host a conference call and live audio webcast on Thursday, February 22, 2024, at 4:30 p.m. ET/1:30 p.m. PT. The live audio webcast may be accessed through the "Events & Presentations" page on the "Investors" section of the Company’s website at View Source A replay of the webcast will be available for 30 days following the live event.

To dial into the call, participants will need to register for the call using the caller registration link. It is recommended that participants dial into the conference call or log into the webcast approximately 10 minutes prior to the call.

Important U.S. Product Information
HEPLISAV-B is indicated for the prevention of infection caused by all known subtypes of hepatitis B virus in adults aged 18 years and older.

For full U.S. Prescribing Information for HEPLISAV-B, click here.

Important U.S. Safety Information (ISI)
Do not administer HEPLISAV-B to individuals with a history of a severe allergic reaction (e.g., anaphylaxis) after a previous dose of any hepatitis B vaccine or to any component of HEPLISAV-B, including yeast.

Appropriate medical treatment and supervision must be available to manage possible anaphylactic reactions following administration of HEPLISAV-B.

Immunocompromised persons, including individuals receiving immunosuppressant therapy, may have a diminished immune response to HEPLISAV-B.

Hepatitis B has a long incubation period. HEPLISAV-B may not prevent hepatitis B infection in individuals who have an unrecognized hepatitis B infection at the time of vaccine administration.

The most common patient-reported adverse reactions reported within 7 days of vaccination were injection site pain (23% to 39%), fatigue (11% to 17%), and headache (8% to 17%).