Blueprint Medicines to Regain Global Rights to GAVRETO® (pralsetinib) from Roche

On February 23, 2023 Blueprint Medicines Corporation (NASDAQ: BPMC) reported that it will regain global commercialization and development rights to GAVRETO (pralsetinib), excluding Greater China, following a decision by Roche to discontinue the collaboration agreement between the companies for GAVRETO for strategic reasons (Press release, Blueprint Medicines, FEB 23, 2023, View Source [SID1234627606]).

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Under the terms of the agreement, the termination will be effective 12 months from the notification date of February 22, 2023. During the transition period, Blueprint Medicines and Roche are mutually committed to ensuring a smooth transition process with no anticipated interruptions or changes to patient access. In addition, the company will explore options to advance and simplify the continued global commercialization and development of GAVRETO.

"At Blueprint Medicines, we are dedicated to driving innovation and changing outcomes for patients with lung cancer. GAVRETO is an important treatment option for patients with RET fusion-positive lung cancer and other RET-altered cancers, and we are committed to ensuring that patients being treated with GAVRETO in the commercial and clinical trial settings continue to have access," said Kate Haviland, Chief Executive Officer of Blueprint Medicines. "Over the next year, we will work alongside Roche to transition the GAVRETO program. In parallel, Blueprint will determine the optimal path forward to bring GAVRETO to patients in a way that maximizes its impact and value. As we do this, we will remain focused on our 2023 goals, with our highest priorities being the anticipated U.S. launch of AYVAKIT (avapritinib) in indolent systemic mastocytosis and the ongoing advancement of our pipeline of investigational medicines."

Since the initiation of the collaboration with Roche in July 2020, Blueprint Medicines has benefited from approximately $1 billion between upfront and milestone payments and from cost-sharing the commercialization and development of GAVRETO. The company anticipates no impact to its 2023 revenue guidance, which includes $40 million to $50 million in collaboration revenues from existing collaborations, or its anticipated operating expenses in 2023. In addition, the company continues to expect that its existing cash, cash equivalents and investments, together with anticipated future product revenues, will provide sufficient capital to enable the company to achieve a self-sustainable financial profile.

About GAVRETO (pralsetinib)

GAVRETO (pralsetinib) is a once-daily oral targeted therapy approved by the U.S. Food and Drug Administration (FDA) for the treatment of three indications: adult patients with metastatic RET fusion-positive NSCLC as detected by an FDA approved test, adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy, and adults and pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate). In addition, GAVRETO has conditional marketing authorization from the European Commission as a monotherapy for the treatment of adults with RET fusion-positive advanced NSCLC not previously treated with a RET inhibitor. GAVRETO is also approved by the National Medical Products Administration (NMPA) of China for the treatment of adult patients with locally advanced or metastatic RET fusion-positive NSCLC after platinum-based chemotherapy, adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant MTC who require systemic therapy, and adult and pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and are radioactive iodine-refractory (if radioactive iodine treatment is appropriate).

Blueprint Medicines has an exclusive collaboration and license agreement with CStone Pharmaceuticals for the development and commercialization of GAVRETO in Greater China, which encompasses Mainland China, Hong Kong, Macau and Taiwan.

GAVRETO is designed to selectively and potently target oncogenic RET alterations, including secondary RET mutations predicted to drive resistance to treatment. For more information, visit GAVRETO.com.

Enlivex Receives Clearance From Spanish Agency of Medicines and Medical Devices For Treatment of Patients with Advanced Solid Malignancies in the Ongoing Allocetra Phase I/II Clinical Trial

On February 23, 2023 Enlivex Therapeutics Ltd. (Nasdaq: ENLV, the "Company"), a clinical-stage macrophage reprogramming immunotherapy company, reported that the Spanish Agency of Medicines and Medical Devices (AEMPS) has authorized the expansion of the Company’s Phase I/II of AllocetraTM in patients with advanced solid malignancies (Press release, Enlivex Therapeutics, FEB 23, 2023, View Source [SID1234627605]). The clearance of the Phase I/II by the AEMPS follows recent announcements by the Company that (i) the study received IND clearance from the U.S. Food And Drug Administration for recruitment of patients in the U.S., (ii) the independent Data Safety Monitoring Board has completed its prespecified data review for the first cohort of patients in the Phase I/II trial and (iii) the Israeli Ministry of Health had reviewed the data and provided regulatory clearance to continue the study and open the subsequent high dose monotherapy and combination cohorts.

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The Phase I/II multi-center clinical trial (clinicaltrials.gov Identifier: NCT05581719) has been designed to evaluate the safety, tolerability and preliminary efficacy of Allocetra alone, and in combination with a PD1 checkpoint inhibitor, in patients with advanced solid tumors.

The Phase I/II trial was initiated following encouraging preclinical studies conducted in collaboration with Yale Cancer Center that showed a substantial, statistically significant survival benefit when Allocetra was combined with a PD1 checkpoint inhibitor in a murine model of ovarian cancer, and additional models that demonstrated statistically significant survival benefit when Allocetra was combined with a PD1 or CTLA-4 checkpoint inhibitors in a murine model of peritoneal mesothelioma.

Einat Galamidi, MD., Vice President, Medical of Enlivex, stated "We are pleased with the AEMPS’ regulatory clearance to expand our clinical trial into Spain. We believe that AllocetraTM has the potential to provide a paradigm shift in treatment of advanced solid tumors, and we look forward to data readouts, including safety and potential indication of effect in patients, currently expected during 2023 and 2024."

ABOUT ALLOCETRA

Allocetra is being developed as a universal, off-the-shelf cell therapy designed to reprogram macrophages into their homeostatic state. Diseases such as solid cancers, sepsis, and many others reprogram macrophages out of their homeostatic state. These non-homeostatic macrophages contribute significantly to the severity of the respective diseases. By restoring macrophage homeostasis, Allocetra has the potential to provide a novel immunotherapeutic mechanism of action for life-threatening clinical indications that are defined as "unmet medical needs", as a stand-alone therapy or in combination with leading therapeutic agents.

Dynavax Reports Fourth Quarter and Full Year 2022 Financial Results and Provides Full Year 2023 Financial Guidance

On February 23, 2023 Dynavax Technologies Corporation (Nasdaq: DVAX), a commercial-stage biopharmaceutical company developing and commercializing innovative vaccines, reported financial results for the fourth quarter and the full year ending December 2022 (Press release, Dynavax Technologies, FEB 23, 2023, View Source [SID1234627602]).

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"In 2022, our team exceeded our strategic goals, achieving record HEPLISAV-B revenue, advancing our clinical pipeline and delivering orders of CpG 1018 adjuvant for the equivalent of hundreds of millions of COVID-19 vaccine doses," said Ryan Spencer, Chief Executive Officer of Dynavax. "Following a year of successful execution on our strategy, we are excited for 2023 and look forward to continuing our trend of significant and sustainable annual HEPLISAV-B revenue growth and overall advancement of our business focused on protecting patients worldwide from infectious diseases."

2023 FINANCIAL GUIDANCE

Dynavax anticipates full-year 2023 revenue and operating expenses to be in the ranges below:

HEPLISAV-B net product revenue between approximately $165 – $185 million
Research and development expenses between approximately $55 – $70 million
Selling, general and administrative expenses between approximately $135 – $155 million
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. and EU 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 achieved record annual net product revenue of $125.9 million for 2022, compared to $61.9 million for 2021, representing annual growth of 104%.
HEPLISAV-B market share in prioritized Integrated Delivery Networks (IDNs) and Clinics increased to approximately 47%, with total market share increasing to approximately 35%, up from approximately 33% and 25%, respectively, at the end of 2021.
Dynavax believes it has begun to see a positive impact on HEPLISAV-B revenue from the expanded ACIP recommendation for adult hepatitis B vaccination which has the potential to expand the market to over $800 million by 2027 with HEPLISAV-B well-positioned to achieve a majority market-share.
CpG 1018 Adjuvant Supply for COVID-19 Vaccines
Dynavax has established a global portfolio of CpG 1018 adjuvant commercial supply agreements (CSAs) supporting the development of COVID-19 vaccines across a variety of vaccine platforms.

CpG 1018 adjuvant achieved annual net product revenue of $587.7 million for 2022, up 57% compared to $375.2 million for 2021.
Due to the successful execution on the pandemic commercial supply agreements and the resulting volume of partners’ overall stockpile, coupled with unknowns about the trajectory of the COVID-19 pandemic, Dynavax believes it will have minimal to as little as zero CpG 1018 adjuvant net product revenues in 2023.
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.

Tetanus, diphtheria and pertussis (Tdap) vaccine program:

In October, the Company presented adult and adolescent safety data from a Phase 1 clinical trial demonstrating the Tdap vaccine candidate was well tolerated without observed safety concerns. Immunogenicity in adults was consistent with the Company’s expectations and support its plan to continue advancement of this clinical program. These clinical results were presented at ID Week 2022.
Data from non-human primate challenge study is anticipated mid-2023.
The Company plans to initiate a human challenge study by the end of 2023.
Shingles vaccine program:

In January 2023, the Company reported top line results from the Phase 1 clinical trial designed to evaluate an investigational shingles vaccine, utilizing different regimens of CpG 1018 adjuvant.
The full Phase 1 data will be submitted for presentation at an upcoming medical meeting in the first half of 2023.
The Company plans to initiate a Phase 1/2 study in early 2024 to evaluate various dose levels of glycoprotein E (gE).
Plague vaccine candidate funded by the Defense Department (DoD):

Part 1 of the Phase 2 clinical trial evaluating the immunogenicity, safety, and tolerability in adults of a plague (rF1V) vaccine candidate adjuvanted with CpG 1018 was successfully completed in January 2023.
Both CpG 1018 adjuvanted arms met the Part 1 primary endpoint and demonstrated a greater than two-fold increase in antibodies over the alum adjuvanted control arm after two doses.
The DoD has approved continuing to Part 2 using a bedside mix of CpG 1018 with the alum adjuvanted rF1V plague vaccine.
FOURTH QUARTER AND FULL YEAR FINANCIAL HIGHLIGHTS

Total Revenue.

Total revenue for the fourth quarter of 2022 was $184.5 million, compared to $195.1 million for the fourth quarter of 2021.
Total revenue for the full year 2022 was $722.7 million, compared to $439.4 million for the full year 2021.
Product Revenue, Net.
HEPLISAV-B

HEPLISAV-B vaccine product revenue, net was $34.9 million for the fourth quarter of 2022, compared to $17.2 million for the fourth quarter of 2021.
HEPLISAV-B vaccine product revenue, net was $125.9 million for the full year 2022, compared to $61.9 million for the full year 2021, representing annual growth of 104%.
CpG 1018 Adjuvant Supply for COVID-19 Vaccines

CpG 1018 adjuvant product revenue, net was $147.2 million in the fourth quarter of 2022, compared to $177.4 million in the fourth quarter of 2021.
CpG 1018 adjuvant product revenue, net was $587.7 million for the full year 2022, compared to $375.2 million for the full year 2021.
Cost of Sales – Product. Cost of sales – product for the fourth quarter of 2022 increased to $77.5 million, compared to $74.0 million for the fourth quarter of 2021. Full year 2022 cost of sales – product was $262.2 million compared to $173.6 million for the full year 2021. The increase was due to higher sales volume for HEPLISAV-B and CpG 1018 adjuvant in 2022.

Research and Development Expenses (R&D). R&D expenses for the fourth quarter of 2022 increased to $12.9 million, compared to $11.1 million for the fourth quarter of 2021. Full year 2022 R&D expenses were $46.6 million compared to $32.2 million for the full year 2021. The increase was primarily driven by continued investments in our product candidates utilizing CpG 1018 adjuvant through pre-clinical and clinical collaborations and additional discovery efforts.

Selling, General, and Administrative Expenses (SG&A). SG&A expenses for the fourth quarter of 2022 increased to $31.0 million, compared to $29.2 million for the fourth quarter of 2021. Full year 2022 SG&A expenses were $131.4 million compared to $100.2 million for the full year 2021. The increase was primarily driven by higher compensation and related personnel costs and an overall increase in targeted commercial and marketing efforts to increase market share and maximize the Centers for Disease Control and Prevention’s Advisory Committee of Immunization Practices (ACIP) universal recommendation.

Net Income. GAAP net income was $67.7 million, or $0.53 per share (basic) and $0.45 per share (diluted) in the fourth quarter of 2022, compared to GAAP net income of $99.8 million, or $0.80 per share (basic) and $0.55 per share (diluted) in the fourth quarter of 2021. GAAP net income was $293.2 million, or $2.32 per share (basic) and $1.97 per share (diluted) for the full year 2022, compared to GAAP net income was $76.7 million, or $0.62 per share (basic) and $0.57 per share (diluted) for the full year 2021.

Cash and Marketable Securities. Cash and marketable securities were $624.4 million as of December 31, 2022.

Conference Call and Webcast Information

Dynavax will host a conference call and live audio webcast on Thursday, February 23, 2023, 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%).

CTI BioPharma To Report Fourth Quarter and Full Year 2022 Financial Results and Provide Corporate Update on Monday, March 6, 2023

On February 23, 2023 CTI BioPharma Corp. (Nasdaq: CTIC), a commercial biopharmaceutical company focused on the development and commercialization of novel targeted therapies for blood-related cancers, reported that its fourth quarter and full year 2022 financial results will be reported on Monday, March 6, 2023, after the close of the financial markets (Press release, CTI BioPharma, FEB 23, 2023, View Source [SID1234627601]). Management will host a webcast and conference call at 4:30 p.m. Eastern Time to discuss the results and provide a corporate update.

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Registration for the live and archived webcast may be accessed on the CTI BioPharma website under the Investors & Media section: Events and Presentations. To participate via telephone, please register in advance using the link provided in the event listing. The Company suggests participants log in 15 minutes in advance of the event.

C4 Therapeutics Reports Fourth Quarter and Full Year 2022 Financial Results and Recent Business Highlights

On February 23, 2023 C4 Therapeutics, Inc. (C4T) (Nasdaq: CCCC), a clinical-stage biopharmaceutical company dedicated to advancing targeted protein degradation science to develop a new generation of small-molecule medicines and transform how disease is treated, reported business highlights and financial results for the year ended December 31, 2022 (Press release, C4 Therapeutics, FEB 23, 2023, View Source [SID1234627600]).

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"2022 was a year of execution that has laid the groundwork for 2023 as we work to progress three clinical programs, with a fourth expected to enter the clinic by year end," said Andrew Hirsch, president and chief executive officer of C4 Therapeutics. "With cash runway through the end of 2024, we look forward to having two clinical readouts in the second half of the year, which have the potential to validate our TORPEDO platform to develop both BiDAC and MonoDAC degraders for patients with difficult-to-treat diseases."

FOURTH QUARTER 2022 AND RECENT HIGHLIGHTS

CFT7455: CFT7455 is an oral degrader of IKZF1/3 for the treatment of multiple myeloma (MM) and non-Hodgkin’s lymphomas (NHL).

Progressed the Phase 1/2 Clinical Trial: In January 2023, opened Arm B2 of the ongoing Phase 1/2 clinical trial, evaluating CFT7455 in combination with dexamethasone for the treatment of MM.
CFT8634: CFT8634 is an oral degrader of BRD9 for the treatment of synovial sarcoma and SMARCB1-null solid tumors.

Encouraging Initial Pharmacokinetic (PK) and Pharmacodynamic (PD) Data: In January 2023, shared PK and PD data from the initial escalation cohorts of the ongoing CFT8634 Phase 1/2 clinical trial demonstrating dose proportional exposure, strong oral bioavailability and deep BRD9 degradation.
CFT1946: CFT1946 is an oral degrader targeting BRAF V600 mutations for the treatment of solid tumors including non-small cell lung cancer (NSCLC), colorectal cancer (CRC) and melanoma.

Dosed First Patient in Phase 1/2 Clinical Trial: In January 2023, dosed the first patient in the CFT1946 Phase 1/2 clinical trial. Trial sites are open and enrolling patients with BRAF V600 mutant cancers including NSCLC, CRC and melanoma.
New Preclinical Data Accepted for Presentation at AACR (Free AACR Whitepaper): Accepted to present new preclinical data on the discovery and characterization of CFT1946 at 2023 AACR (Free AACR Whitepaper) Annual Meeting.
KEY UPCOMING MILESTONES

CFT7455: Present Phase 1 dose escalation data from the Phase 1/2 clinical trial of Arm B1, evaluating CFT7455 as a monotherapy in MM, in the second half of 2023.
CFT8634: Present Phase 1 dose escalation data from the Phase 1/2 clinical trial in the second half of 2023 in synovial sarcoma and SMARCB1-null solid tumors.
CFT1946: Continue site activation and patient enrollment of the dose escalation portion of the CFT1946 Phase 1/2 clinical trial in BRAF V600 mutant solid tumors. Present new preclinical data on the discovery and characterization of CFT1946 at 2023 AACR (Free AACR Whitepaper) Annual Meeting in April.
CFT8919: Submit an Investigational New Drug (IND) application for CFT8919 for the treatment of NSCLC in the first half of 2023.
UPCOMING INVESTOR EVENTS

March 6, 2023: Management will participate in the Cowen & Co. 43rd Annual Health Care Conference.
FULL YEAR 2022 FINANCIAL RESULTS

Revenue: Total revenue for the year ended December 31, 2022 was $31.1 million, compared to $45.8 million for the year ended December 31, 2021. Total revenue reflects revenue recognized under collaboration agreements with Roche, Biogen and Calico. The decrease in revenue is primarily due to a one-time cumulative recognition during the year ended December 31, 2021 for all of the previously unrecognized revenue allocated to the BRAF program upon the termination of the Roche agreement related to that target.

Research and Development (R&D) Expense: R&D expense for the year ended December 31, 2022 was $117.8 million, compared to $94.7 million for the year ended December 31, 2021. The increase in R&D expense was primarily attributable to clinical costs for CFT7455 and CFT8634, increased external costs, and internal workforce expenses to support the increased level of clinical trial activity.

General and Administrative (G&A) Expense: G&A expense for the year ended December 31, 2022 was $42.8 million, compared to $33.3 million for the year ended December 31, 2021. The increase in G&A expense was primarily attributable to the full-year 2022 impact of the build-out of our general and administrative team to support business growth.

Net Loss and Net Loss per Share: Net loss for the year ended December 31, 2022 was $128.2 million, compared to $83.9 million for the year ended December 31, 2021. Net loss per share for the year ended December 31, 2022 was $2.62, compared to $1.82 for the year ended December 31, 2021.

Cash Position and Financial Guidance: Cash, cash equivalents and marketable securities as of December 31, 2022 was $337.1 million, compared to $451.5 million as of December 31, 2021. C4T expects that its cash, cash equivalents and marketable securities as of December 31, 2022, together with anticipated collaboration expense reimbursements, but excluding any collaboration option or milestone payments, will enable the company to fund its operating plan to the end of 2024.