On February 29, 2024 Lisata Therapeutics, Inc. (Nasdaq: LSTA) ("Lisata" or the "Company"), a clinical-stage pharmaceutical company developing innovative therapies for the treatment of advanced solid tumors and other serious diseases, reported a business update and announced financial results for the twelve months ended December 31, 2023 (Press release, Lisata Therapeutics, FEB 29, 2024, View Source [SID1234640654]).

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"2023 was a testament to our unwavering commitment to operational excellence and focused, efficient development. Our entire organization worked seamlessly to achieve significant milestones in the advancement of our lead investigational product, LSTA1," stated David J. Mazzo, Ph.D., President and Chief Executive Officer of Lisata. "Throughout 2024, we look to maintain and even build on this momentum as we project numerous data announcements in the coming 12 to 24 months, including the release of topline data from the Phase 2b ASCEND trial ("ASCEND") later this year. We intend to use these results to explore conditional approvals in several jurisdictions around the world and/or to design an optimized Phase 3 program in pancreatic ductal adenocarcinoma. Concurrently, we remain committed to the advancement of our other active and planned studies investigating LSTA1 in combination with a variety of standard-of-care regimens across multiple solid tumor indications."
Dr. Mazzo added, "Our prudent stewardship of our financial resources allows us to reaffirm our projection that our cash runway extends into early 2026 and funds all our trials until data completion. More than ever, we remain confident in our ability to execute our development activities efficiently with the goal of reaching significant clinical milestones at the earliest possible juncture."

Development Portfolio Highlights

LSTA1 as a treatment for solid tumors in combination with other anti-cancer agents

LSTA1 is an investigational drug designed to activate the CendR uptake pathway that allows co-administered or molecularly bound anti-cancer drugs to target and penetrate solid tumors more effectively. LSTA1 is designed to actuate this active transport system in a tumor-specific manner, resulting in systemically co-administered anti-cancer drugs more efficiently penetrating and accumulating in the tumor, to the exclusion of normal tissues. In preclinical models, LSTA1 has also shown the ability to modify the tumor microenvironment, leading to the expectation that tumors will become more susceptible to immunotherapies and inhibiting the metastatic cascade (i.e., the spread of cancer to other parts of the body). Lisata and its development collaborators have amassed significant non-clinical data demonstrating enhanced delivery of a range of existing and emerging anti-cancer therapies, including chemotherapeutics, immunotherapies, and RNA-based therapeutics. To date, LSTA1 has also demonstrated favorable safety, tolerability, and activity in completed and ongoing clinical trials designed to test its ability to enhance delivery of standard-of-care chemotherapy for metastatic pancreatic cancer. Currently, LSTA1 is the subject of multiple ongoing or planned Phase 2a and 2b clinical studies being conducted globally in a variety of solid tumor types in combination with a variety of anti-cancer regimens. As previously announced, LSTA1 has been granted orphan drug designation for pancreatic cancer in the U.S. and Europe as well as for glioblastoma multiforme ("GBM") in the U.S. The product candidate has also received a Fast Track designation from the U.S. Food and Drug Administration for pancreatic cancer.
◦ASCEND: Phase 2b double-blind, randomized, placebo-controlled clinical trial evaluating two dosing regimens of LSTA1 in combination with gemcitabine/nab-paclitaxel standard-of-care ("SOC") chemotherapy

in patients with metastatic pancreatic ductal adenocarcinoma ("mPDAC"). Cohort A of the study receives a single dose of 3.2 mg/kg LSTA1 essentially simultaneously with SOC, while Cohort B is identical to Cohort A, but with a second dose of 3.2mg/kg of LSTA1 given 4 hours after the first. The trial is being conducted at 25 sites in Australia and New Zealand led by the Australasian Gastro-Intestinal Trials Group in collaboration with the University of Sydney and with the National Health and Medical Research Council Clinical Trial Centre at the University of Sydney as the Coordinating Centre. The conclusion of a planned interim futility analysis in 2023 by the Independent Data Safety Monitoring Committee ("IDSMC") was that the conditions for futility were not met and that the study should proceed to completion. With trial enrollment completed in the fourth quarter of 2023, Lisata expects topline data from the 98 patients assigned to Cohort A of the study to be reported in the fourth quarter of 2024 and the complete data set of all 158 patients from the study to be available by mid-2025
◦BOLSTER: Phase 2a double-blind, placebo-controlled, multi-center, randomized basket trial in the U.S., Europe, Canada, and Australia evaluating LSTA1 in combination with standards-of-care in second line head and neck cancer and first line cholangiocarcinoma. The trial is actively enrolling with enrollment completion expected by the end of 2024.
◦CENDIFOX: Phase 1b/2a open-label trial in the U.S. of LSTA1 in combination with neoadjuvant FOLFIRINOX based therapies in pancreatic, colon and appendiceal cancers. The trial continues to make steady progress with enrollment completion expected by the end of the second quarter of 2024.
◦Qilu Pharmaceutical, the licensee of LSTA1 in the Greater China territory, is currently evaluating LSTA1 in combination with gemcitabine and nab-paclitaxel in a Phase 1b/2a open-label trial in China. During the 2023 ASCO (Free ASCO Whitepaper) Annual Meeting, Qilu Pharmaceutical presented an abstract sharing preliminary data from the study which corroborated previously reported findings from the Phase 1b/2a trial of LSTA1 plus gemcitabine and nab-paclitaxel conducted in Australia in patients with mPDAC. Final data is expected by the end of the second quarter of 2024, with the initiation of Phase 2 in China expected shortly thereafter.
◦iLSTA: Phase 1b/2a randomized, single-blind, single-center, safety and pharmacodynamic trial in Australia evaluating LSTA1 in combination with the checkpoint inhibitor, durvalumab, plus standard-of-care gemcitabine and nab-paclitaxel chemotherapy versus standard-of-care alone in patients with locally advanced non-resectable PDAC. Enrollment completion is expected in the second half of 2024.
◦Lisata-funded Phase 2a, double-blind, placebo-controlled, randomized, proof-of-concept study evaluating LSTA1 in combination with standard-of-care temozolomide versus temozolomide alone in patients with newly diagnosed GBM is being conducted across multiple sites in Estonia and Latvia and is targeted to enroll 30 patients with a randomization of 2:1 in favor of the LSTA1 treatment group.
Full Year 2023 Financial Highlights
For the year ended December 31, 2023, operating expenses totaled $25.7 million compared to $57.6 million for the year ended December 31, 2022, representing a decrease of $31.9 million or 55.4%. Excluding the in-process research and development expense of $30.4 million associated with the merger with Cend Therapeutics, Inc. (the "Merger"), operating expenses decreased by $1.5 million or 5.5% compared to the year ended December 31, 2022.
Research and development expenses were approximately $12.7 million for the year ended December 31, 2023, compared to $13.1 million for the year ended December 31, 2022, representing a decrease of approximately $0.3 million, or 2.5%. This decrease was primarily due to lower costs associated with our LSTA1 programs in the current year versus our legacy CD34+ cell therapy technology programs in the prior year. Current year expenses were associated with study activities for LSTA1 Phase 2a proof-of-concept Bolster trial in various solid tumors in combination with the corresponding standards of care, enrollment activities for the LSTA1 Phase 2b ASCEND study, chemistry, manufacturing and control activities for LSTA1 and study start up activities for the LSTA1 Phase 2a study for the treatment of GBM.
General and administrative expenses were approximately $13.0 million for the year ended December 31, 2023, compared to $14.1 million for the year ended December 31, 2022, representing a decrease of approximately $1.2 million or 8.3%. This decrease was primarily due to non-recurring Merger related costs in the prior year, a decrease in
equity expense due to prior year performance stock unit vesting, Merger option assumption expense and departing board member restricted stock unit vesting, lower annual stockholder meeting expenses and a decrease in directors and officers insurance premiums, partially offset by severance costs associated with the elimination of the Chief Business Officer position on May 1, 2023.
Overall, net losses were $20.8 million and $54.2 million for the years ended December 31, 2023 and 2022, respectively.
Balance Sheet Highlights
As of December 31, 2023, Lisata had cash, cash equivalents, and marketable securities of approximately $50.5 million. Based on its current expected capital needs, the Company believes that its projected capital will fund its current proposed operations into early 2026, encompassing anticipated data milestones from all its ongoing and planned clinical trials.

Conference Call Information

Lisata will hold a live conference call on Thursday, February 29, 2024 at 4:30 p.m. Eastern time to discuss financial results, provide a business update and answer questions.
Those wishing to participate must register for the conference call by way of the following link: CLICK HERE TO REGISTER. Registered participants will receive an email containing conference call details with dial-in options. To avoid delays, we encourage participants to dial into the conference call fifteen minutes ahead of the scheduled start time.
A live webcast of the call will also be accessible under the Investors & News section of Lisata’s website and will be available for replay beginning two hours after the conclusion of the call for 12 months.

On February 29, 2024 BlossomHill Therapeutics, Inc., a biotechnology company focused on the design and development of small molecule medicines for treating cancer and autoimmune diseases, reported the closing of a $100 million Series B financing round (Press release, BlossomHill Therapeutics, FEB 29, 2024, View Source [SID1234640653]). The round was led by Colt Ventures with participation from new and existing investors, including Cormorant Asset Management, OrbiMed, Vivo Capital, Hercules BioVentures Partners LLC, Plaisance Capital Management LLC and H&D Asset Management, among others. In conjunction with the financing round, Sundeep Agrawal, M.D., General Partner at Colt Ventures, and Timothy Stubbs, M.D., Principal at Vivo Capital, will join the BlossomHill Board of Directors.

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This financing brings the total capital raised by the company to $173 million. BlossomHill will use the proceeds to advance its pipeline of multiple in-house discovery and development programs for multiple high-need cancers and autoimmune diseases into the clinic.

"We appreciate the strong support from our new and existing investors in this round of financing," said J. Jean Cui, Ph.D., President and Chief Executive Officer of BlossomHill Therapeutics. "This will be a pivotal year for BlossomHill as we move our first two oncology programs into phase 1 clinical trials, advance several programs forward to IND enabling studies, and continue to build our already very deep pipeline of oncology and autoimmune discovery programs."

BlossomHill is a drug design company redefining precision medicine to make a leap forward in life expectancy and quality of life for patients, creating novel chemical entities that seek to address on- and off-target resistance mechanisms. Combining human intelligence, creative thinking, and proven drug design expertise, the company is developing small molecules with the potential to redefine the gold standard for cancer and autoimmune disease treatment.

"It is a privilege to partner with Dr. Jean Cui and her team at BlossomHill. We have been highly impressed with her drug design capabilities and the innovative pipeline she has built," said Sundeep Agrawal, M.D., General Partner at Colt Ventures. "Jean has an outstanding track record of designing three FDA-approved cancer drugs, and we look forward to supporting the company’s next phase of development."

BlossomHill was co-founded in June 2020 by renowned drug designer and chemist Dr. Jean Cui, who is responsible for the design of the FDA-approved drugs crizotinib (XALKORI), lorlatinib (LOBRENA) and repotrectinib (AUGTYRO) and biotech business veteran, Y. Peter Li, Ph.D., M.B.A. Dr. Cui and Dr. Li were also the co-founders of Turning Point Therapeutics, Inc., which was acquired by Bristol Myers Squibb in June 2022.

"We are excited to continue to support BlossomHill Therapeutics’ creative, trailblazing drug development team in its mission of bringing potentially best-in-class drug treatment to meaningfully improve patient lives," said Bihua Chen, Founder of Cormorant Asset Management.

"Since its founding, the company has made rapid progress on its drug discovery programs, and we look forward to the generation of clinical data as BlossomHill enters its next phase," added Carl Gordon, Ph.D.,Managing Partner, OrbiMed Advisors.

On February 29, 2024 BeiGene, Ltd. (Nasdaq: BGNE; HKEX: 06160; SSE: 688235), a global oncology company, reported a new matching adjusted indirect comparison (MAIC) of the efficacy of BRUKINSA (zanubrutinib) versus acalabrutinib in relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) based on data from the Phase 3 ALPINE and Phase 3 ASCEND trials (Press release, BeiGene, FEB 29, 2024, View Source [SID1234640652]). The analysis suggests a progression-free survival and complete response advantage for BRUKINSA versus acalabrutinib, as well as potentially improved overall survival. These data will be presented during the 28th Annual International Congress on Hematologic Malignancies in Miami from February 29 – March 3.

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"The CLL landscape is evolving rapidly, and this MAIC provides timely comparative effectiveness data for physicians, and reinforces zanubrutinib role as a foundational CLL treatment via a robust evaluation of the efficacy in the ASCEND and ALPINE studies; the presented analysis not only accounts for differences in key patient characteristics, but also clarifies the impact COVID-19 may have had on study outcomes," said Mazyar Shadman, M.D. M.P.H, Study Author and Innovators Network Endowed Chair, Associate Professor of Hematology and Oncology, Lymphoid Malignancies and Immunotherapy, Fred Hutch Cancer Center and University of Washington. "Head-to-head randomized clinical trials are the gold standard when it comes to evaluating the potential impact of individual treatments for patients. MAICs are intended to be hypothesis-generating, provided they are conducted with appropriate rigor to minimize potential biases."

In this MAIC, individual patient-level data from ALPINE was matched against the aggregate data from ASCEND. An unanchored MAIC was used due to the lack of a common comparator arm between the ALPINE and ASCEND trials. Given the differences in the timing of the studies, with respect to the onset of the COVID-19 pandemic, the analysis adjusted for the impact of COVID-19 in the ALPINE study.

In a previously published MAIC of BRUKINSA versus acalabrutinib,1 there were significant limitations that precluded a robust efficacy comparison, including the exclusion of data from the final analysis of ALPINE, lack of adjustment for the impact of COVID-19 on the outcomes, lack of adjustment for key differences in patient characteristics, the effective sample size, and the exclusion of complete response rate and overall survival from the analysis.

"BeiGene is committed to continuing to further our understanding of the efficacy and safety of our therapies and their potential to help patients among other options," said Mehrdad Mobasher, M.D., M.P.H., Chief Medical Officer, Hematology at BeiGene. "This MAIC addresses key questions raised in a previously published analysis, presenting a more holistic representation of the efficacy associated with BRUKINSA versus acalabrutinib in relapsed or refractory chronic lymphocytic leukemia setting."

BRUKINSA is the only Bruton’s tyrosine kinase (BTK) inhibitor to demonstrate progression-free survival superiority vs ibrutinib in R/R CLL, as observed in the ALPINE trial.2 Acalabrutinib has demonstrated improvement in progression-free survival vs rituximab plus idelalisib/bendamustine in R/R CLL in the ASCEND trial and has also demonstrated progression-free survival noninferiority vs ibrutinib R/R CLL patients with chromosome 17p or 11q deletions in the ELEVATE-RR trial.3,4

The MAIC suggests that investigator-assessed progression-free survival was improved for BRUKINSA versus acalabrutinib in both the unadjusted population (HR=0.77 [95%CI: 0.55-1.07]), as well as the base case adjusted population (HR=0.68 [95%CI: 0.46-0.99]). Additionally, the odds ratio (OR) for complete response favored BRUKINSA over acalabrutinib in the unadjusted (OR=2.88 [95%CI: 1.18-7.02]) and base case adjusted populations (OR=2.90; [95%CI: 1.13-7.43]). Results for the sensitivity analysis were consistent with the base case. The overall survival trend remained consistently in favor of BRUKINSA. For additional details of the analysis, please refer to the full poster presentation.

While MAIC analyses can be hypotheses-generating, in the absence of head-to-head data, the safety of a drug may be best evaluated using all available evidence across indications. A recent independent Mayo Clinic meta-analysis of 61 trials involving 6,959 patients who received ibrutinib plus an anti-CD20 antibody, acalabrutinib, and BRUKINSA extensively analyzed the adverse event profiles of the two therapies across several indications and reported key differences in the safety profiles of the two treatments.5

BRUKINSA is approved in 70 markets, including the U.S., China, EU, Great Britain, Canada, Australia, South Korea and Switzerland in selected indications, and it is under development for additional indications globally. The global BRUKINSA development program includes more than 5,000 subjects enrolled to date in 29 countries and regions.

About MAICs

Match adjusted indirect comparisons are intended to be hypothesis generating, and do not establish superior efficacy or safety of one drug over another. Results should be viewed in the context of study limitations and available clinical data.

About ALPINE

ALPINE is a randomized, global, Phase 3 trial (NCT03734016) comparing BRUKINSA with ibrutinib in previously treated patients with R/R CLL or small lymphocytic lymphoma (SLL). In the trial, a total of 652 patients across Europe (60%), the United States (17%), China (14%), and New Zealand and Australia (9%) were randomized to receive BRUKINSA (160 mg orally twice daily) or ibrutinib (420 mg orally once daily) until disease progression, death, or unacceptable toxicity.

The primary endpoint of overall response rate (ORR) was assessed by both investigator and independent review committee (IRC) using the modified 2008 iwCLL guidelines, with modification for treatment-related lymphocytosis for patients with CLL, and as per Lugano Classification for non-Hodgkin’s lymphoma for patients with SLL. Key secondary endpoints included PFS and the rate of atrial fibrillation or flutter; other secondary endpoints included duration of response, overall survival, and incidence of adverse events. There was a pre-specified hierarchical testing of non-inferiority followed by superiority for ORR as assessed by investigator and IRC. As ORR superiority was demonstrated, progression-free survival was tested for noninferiority and superiority under hierarchical testing.

In an extended follow-up of the ALPINE study at a median follow-up of 39 months, BRUKINSA showed sustained PFS improvement versus ibrutinib (HR: 0.68 [95% CI, 0.53-0.86] P=0.0011) among R/R CLL/SLL patients, with durable PFS benefit observed across key subgroups, including patients with 17p deletion or TP53 mutation (HR: 0.52 [95% CI, 0.33-0.83] P=0.0047). PFS benefit was consistent across multiple sensitivity analyses, demonstrating that PFS advantage with BRUKINSA was primarily driven by efficacy, and not better tolerability. The overall safety and tolerability profile was consistent with previous ALPINE analyses, including persistently lower rates of cardiovascular events reported with BRUKINSA. The most commonly reported treatment emergent adverse events (≥20%) with BRUKINSA were COVID-19-related infection, neutropenia, hypertension, and upper respiratory tract infection.6

About BRUKINSA (zanubrutinib)

BRUKINSA is a small molecule inhibitor of BTK designed to deliver complete and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity. With differentiated pharmacokinetics compared with other approved BTK inhibitors, BRUKINSA has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease-relevant tissues.

U.S. Indications and Important Safety Information for BRUKINSA (zanubrutinib)

INDICATIONS

BRUKINSA is a kinase inhibitor indicated for the treatment of adult patients with:

Chronic lymphocytic leukemia or small lymphocytic lymphoma
Waldenström’s macroglobulinemia
Mantle cell lymphoma (MCL) who have received at least one prior therapy
Relapsed or refractory marginal zone lymphoma (MZL) who have received at least one anti-CD20-based regimen
The MCL and MZL indications are approved under accelerated approval based on overall response rate. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Hemorrhage

Fatal and serious hemorrhage has occurred in patients with hematological malignancies treated with BRUKINSA monotherapy. Grade 3 or higher hemorrhage, including intracranial and gastrointestinal hemorrhage, hematuria and hemothorax have been reported in 3.6% of patients treated with BRUKINSA monotherapy in clinical trials, with fatalities occurring in 0.3% of patients. Bleeding of any grade, excluding purpura and petechiae, occurred in 30% of patients.

Bleeding has occurred in patients with and without concomitant antiplatelet or anticoagulation therapy. Coadministration of BRUKINSA with antiplatelet or anticoagulant medications may further increase the risk of hemorrhage.

Monitor for signs and symptoms of bleeding. Discontinue BRUKINSA if intracranial hemorrhage of any grade occurs. Consider the benefit-risk of withholding BRUKINSA for 3-7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding.

Infections

Fatal and serious infections (including bacterial, viral, or fungal infections) and opportunistic infections have occurred in patients with hematological malignancies treated with BRUKINSA monotherapy. Grade 3 or higher infections occurred in 24% of patients, most commonly pneumonia (11%), with fatal infections occurring in 2.9% of patients. Infections due to hepatitis B virus (HBV) reactivation have occurred.

Consider prophylaxis for herpes simplex virus, pneumocystis jiroveci pneumonia, and other infections according to standard of care in patients who are at increased risk for infections. Monitor and evaluate patients for fever or other signs and symptoms of infection and treat appropriately.

Cytopenias

Grade 3 or 4 cytopenias, including neutropenia (22%), thrombocytopenia (8%) and anemia (7%) based on laboratory measurements, developed in patients treated with BRUKINSA monotherapy. Grade 4 neutropenia occurred in 11% of patients, and Grade 4 thrombocytopenia occurred in 2.8% of patients.

Monitor complete blood counts regularly during treatment and interrupt treatment, reduce the dose, or discontinue treatment as warranted. Treat using growth factor or transfusions, as needed.

Second Primary Malignancies

Second primary malignancies, including non-skin carcinoma, have occurred in 13% of patients treated with BRUKINSA monotherapy. The most frequent second primary malignancy was non-melanoma skin cancer reported in 7% of patients. Other second primary malignancies included malignant solid tumors (5%), melanoma (1.2%), and hematologic malignancies (0.5%). Advise patients to use sun protection and monitor patients for the development of second primary malignancies.

Cardiac Arrhythmias

Serious cardiac arrhythmias have occurred in patients treated with BRUKINSA. Atrial fibrillation and atrial flutter were reported in 3.7% of 1550 patients treated with BRUKINSA monotherapy, including Grade 3 or higher cases in 1.7% of patients. Patients with cardiac risk factors, hypertension and acute infections may be at increased risk. Grade 3 or higher ventricular arrhythmias were reported in 0.2% of patients.

Monitor for signs and symptoms of cardiac arrhythmias (e.g. palpitations, dizziness, syncope, dyspnea, chest discomfort), manage appropriately, and consider the risks and benefits of continued BRUKINSA treatment.

Embryo-Fetal Toxicity

Based on findings in animals, BRUKINSA can cause fetal harm when administered to a pregnant woman. Administration of zanubrutinib to pregnant rats during the period of organogenesis caused embryo-fetal toxicity, including malformations at exposures that were 5 times higher than those reported in patients at the recommended dose of 160 mg twice daily. Advise women to avoid becoming pregnant while taking BRUKINSA and for 1 week after the last dose. Advise men to avoid fathering a child during treatment and for 1 week after the last dose. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.

Adverse Reactions

In this pooled safety population, the most common adverse reactions, including laboratory abnormalities, in ≥30% of patients who received BRUKINSA (N=1550) included decreased neutrophil count (42%), upper respiratory tract infection (39%), decreased platelet count (34%), hemorrhage (30%), and musculoskeletal pain (30%).

Drug Interactions

CYP3A Inhibitors: When BRUKINSA is co-administered with a strong CYP3A inhibitor, reduce BRUKINSA dose to 80 mg once daily. For coadministration with a moderate CYP3A inhibitor, reduce BRUKINSA dose to 80 mg twice daily.

CYP3A Inducers: Avoid coadministration with strong or moderate CYP3A inducers. Dose adjustment may be recommended with moderate CYP3A inducers.

Specific Populations

Hepatic Impairment: The recommended dose of BRUKINSA for patients with severe hepatic impairment is 80 mg orally twice daily.

Please see full U.S. Prescribing Information and U.S. Patient Information.

On February 29, 2024 Ariceum Therapeutics (Ariceum), a private biotech company developing radiopharmaceutical products for the diagnosis and treatment of certain hard-to-treat cancers, reported that it has received approval from the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) to undertake a Phase 1 clinical trial (CITADEL-123) of 123I-ATT001, its Iodine-123 labelled PARP inhibitor, in patients with recurrent glioblastoma (Press release, Ariceum Therapeutics, FEB 29, 2024, View Source [SID1234640651]).

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The authorisation follows Ariceum’s submission of a Clinical Trial Authorisation (CTA) application to the MHRA in December 2023 with the Phase 1 study expected to commence in the UK in June 2024. Ariceum is the first company to sponsor a clinical trial of Auger therapy for recurrent glioblastoma, an aggressive form of brain cancer.

Manfred Rüdiger, Chief Executive Officer at Ariceum Therapeutics, said: "It is a tremendous achievement for Ariceum to receive CTA approval by the MHRA so soon after submission. Glioblastoma is the most common and most aggressive type of malignant brain tumour in adults, with a very poor prognosis for survival and currently no cure. Following the integration of Theragnostics into Ariceum and promising pre-clinical results, we welcome the opportunity to be the first company to trial Auger therapy for this indication and we plan to explore other solid tumour indications in the future."

Dr Austin Smith, Medical Oncologist advising Ariceum Therapeutics, commented: "The CITADEL-123 study will allow us to demonstrate the safety and efficacy of ATT001 as a potential treatment option to address the high unmet medical need of patients with Glioblastoma. We are thankful for the continued collaboration with the team at UCLH, led by Dr Paul Mulholland and the support of the patient advocacy group, Braintrust – the brain cancer people."

ATT001 delivers its radioisotope payload, Iodine-123, in a highly targeted way to cancer cells expressing PARP, an enzyme they use to repair its DNA. This radioisotope emits low energy Auger electrons, which deposit their energy over short distances, making them particularly useful for causing lethal damage to cancer cells while sparing healthy tissue. An additional benefit of using Iodine-123 is that this isotope is more widely available than others, being produced in a regular cyclotron. Ariceum in parallel is also exploring 123I-ATT001 in other solid tumour indications, as PARP is a validated target, highly expressed in several other cancers.

On February 29, 2024 Arbutus Biopharma Corporation (Nasdaq: ABUS) ("Arbutus" or the "Company"), a clinical-stage biopharmaceutical company leveraging its extensive virology expertise to develop a functional cure for people with chronic hepatitis B virus (cHBV) infection, reported fourth quarter and year end 2023 financial results and provides a corporate update (Press release, Arbutus Biopharma, FEB 29, 2024, View Source [SID1234640650]).

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"I anticipate that 2024 will be a productive year for Arbutus as we continue to advance the development of our HBV assets: imdusiran, our RNAi therapeutic, and AB-101, our oral checkpoint inhibitor," said Michael J. McElhaugh, Interim President and Chief Executive Officer of Arbutus Biopharma. "To date, we have dosed more than 170 HBV patients with imdusiran and continue to see notable and sustained reductions in surface antigen. We believe that a combination therapy that reduces surface antigen, suppresses HBV DNA and boosts the host immune response will be necessary to functionally cure HBV. We are currently evaluating imdusiran with other immune modulators and expect multiple data readouts this year, including the potential to see undetectable surface antigen at end of treatment. These trials, in addition to our plans to initiate an imdusiran + durvalumab clinical trial, will help inform our later stage clinical development program in addition to the dose and dosing duration for AB-101, potentially expediting imdusiran + AB-101 combinations."

2024 Clinical Development Milestones

Imdusiran (AB-729, RNAi Therapeutic)   

AB-729-201 is a Phase 2a clinical trial that is evaluating the safety, tolerability and antiviral activity of the combination of imdusiran, nucleos(t)ide analogue (NA) therapy and pegylated interferon alfa-2a (IFN) in patients with cHBV. Preliminary data presented at the EASL Congress in June 2023 suggest that the addition of IFN to imdusiran was generally well-tolerated and appears to result in continued HBsAg declines in some patients. Arbutus plans to announce end-of-treatment data from this trial in the first half of 2024.
AB-729-202 is a Phase 2a clinical trial that is evaluating the safety and immunogenicity of imdusiran, NA therapy and Barinthus Bio’s (formerly Vaccitech plc) VTP-300, an HBV antigen-specific immunotherapy. Preliminary data presented at AASLD – The Liver Meeting in November 2023 showed that the combination of imdusiran and VTP-300 provided a meaningful reduction of HBsAg levels that are maintained well below baseline. In addition, a subset of patients given imdusiran and then VTP-300 showed early signs of immune activation. Arbutus plans to announce end-of-treatment data from this portion of the trial in the first half of 2024.
AB-729-202 was amended to include an additional cohort of 20 patients who will receive imdusiran plus NA therapy for 24 weeks followed by VTP-300 plus up to two low doses of nivolumab, an approved anti-PD-1 monoclonal antibody. Preliminary data from this additional cohort are expected in the second half of 2024.
AB-729-203 is a Phase 2a clinical trial that Arbutus intends to initiate in the first half of 2024 to evaluate the safety, tolerability and antiviral activity of intermittent low doses of durvalumab, an approved anti-PD-L1 monoclonal antibody in combination with imdusiran and NA therapy. Insights gained from this clinical trial and the amended portion of the AB-729-202 clinical trial with nivolumab, may inform dosing for the planned imdusiran plus AB-101 Phase 2 clinical trial.
AB-101 (Oral PD-L1 Inhibitor)  

AB-101-001 is a Phase 1a/1b double-blind, randomized, placebo-controlled clinical trial designed to investigate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single- and multiple-ascending oral doses of AB-101 for up to 28 days in healthy subjects and patients with cHBV. Arbutus is advancing AB-101 into part two of this clinical trial which involves dosing healthy subjects with multiple-ascending doses of AB-101. Arbutus expects to report preliminary data from the healthy subject portion of this clinical trial, including target engagement and receptor occupancy data, in the first half of 2024.
LNP Litigation Update:

Arbutus continues to protect and defend its intellectual property, which is the subject of the on-going lawsuits against Moderna and Pfizer/BioNTech. The Company is seeking fair compensation for Moderna’s and Pfizer/BioNTech’s use of its patented LNP technology that was developed with great effort and at a great expense, without which Moderna and Pfizer/BioNTech’s COVID-19 vaccines would not have been successful. With respect to the Moderna lawsuit, fact discovery is on-going and the claim construction hearing occurred on February 8, 2024. According to the Court Scheduling Order, which was issued on March 21, 2023, the court is expected to issue its claim construction order within 60 days of conclusion of the claim construction hearing. Expert testimony and depositions will then follow. A trial date has been set for April 21, 2025 and is subject to the Court’s availability. The lawsuit against Pfizer/BioNTech is ongoing and a date for a claim construction hearing has not been set.
Financial Results

Cash, Cash Equivalents and Investments

As of December 31, 2023, the Company had cash, cash equivalents and investments in marketable securities of $132.3 million compared to $184.3 million as of December 31, 2022. During the year ended December 31, 2023, the Company used $85.9 million in operating activities, which was partially offset by $29.9 million of net proceeds from the issuance of common shares under its "at-the-market" offering program. The Company expects its 2024 net cash burn to range from between $63 million to $67 million, excluding any proceeds received from its "at the market" offering program. The Company believes its cash, cash equivalents and investments in marketable securities of $132.3 million as of December 31, 2023, are sufficient to fund its operations into the first quarter of 2026.

Revenue

Total revenue was $18.1 million for the year ended December 31, 2023, compared to $39.0 million for the same period in 2022. The decrease of $20.9 million was due primarily to a decrease in revenue recognition from the Company’s license agreement with Qilu, the Company’s collaboration partner in China, Hong Kong, Macau and Taiwan, based on a decrease in employee labor hours expended by the Company during 2023 compared to 2022 to perform its manufacturing obligations under the license agreement. Additionally, license royalty revenues decreased in 2023 compared to 2022 due to a decrease in Alnylam’s sales of ONPATTRO.

Operating Expenses

Research and development expenses were $73.7 million for the year ended December 31, 2023 compared to $84.4 million for the same period in 2022. The decrease of $10.7 million was due primarily to: (i) a decrease in manufacturing expenses associated with supplying drug for the Company’s clinical trials; and (ii) a decrease in clinical expenses due to the discontinuation of the Company’s AB-836 program in 2022; partially offset by (iii) an increase in clinical expenses for the Company’s ongoing AB-101 Phase 1a/1b clinical trial in 2023. General and administrative expenses were $22.5 million for the year ended December 31, 2023, compared to $17.8 million for the same period in 2022. This increase was due primarily to an increase in legal fees, non-cash stock-based compensation expense and employee compensation costs.

Net Loss

For the year ended December 31, 2023, our net loss was $72.8 million, or a loss of $0.44 per basic and diluted common share, as compared to a net loss of $69.5 million, or a loss of $0.46 per basic and diluted common share, for the year ended December 31, 2022.

Outstanding Shares

As of December 31, 2023, the Company had 169.9 million common shares issued and outstanding, as well as 20.4 million stock options and unvested restricted stock units outstanding. Roivant Sciences Ltd. owned approximately 23% of the Company’s outstanding common shares as of December 31, 2023.

UNAUDITED CONDENSED CONSOLIDATED STATEMENTS OF LOSS
(in thousands, except share and per share data)

Year Ended December 31,
2023 2022
Revenue
Collaborations and licenses $ 14,274 $ 31,366
Non-cash royalty revenue 3,867 7,653
Total revenue 18,141 39,019
Operating expenses
Research and development 73,700 84,408
General and administrative 22,475 17,834
Change in fair value of contingent consideration 69 2,233
Total operating expenses 96,244 104,475
Loss from operations (78,103 ) (65,456 )
Other income (loss)
Interest income 5,688 2,192
Interest expense (459 ) (1,726 )
Foreign exchange gain 25 (22 )
Total other income 5,254 444
Loss before income taxes (72,849 ) (65,012 )
Income tax expense — (4,444 )
Net loss $ (72,849 ) $ (69,456 )
Net loss per common share
Basic and diluted $ (0.44 ) $ (0.46 )
Weighted average number of common shares
Basic and diluted 165,960,379 150,939,337

UNAUDITED CONDENSED CONSOLIDATED BALANCE SHEETS
(in thousands)

December 31,
2023 December 31,
2022
Cash, cash equivalents and marketable securities, current $ 126,003 $ 146,913
Accounts receivable and other current assets 6,024 4,226
Total current assets 132,027 151,139
Property and equipment, net of accumulated depreciation 4,674 5,070
Investments in marketable securities, non-current 6,284 37,363
Right of use asset 1,416 1,744
Other non-current assets — 103
Total assets $ 144,401 $ 195,419

Accounts payable and accrued liabilities $ 10,271 $ 16,029
Deferred license revenue, current 11,791 16,456
Lease liability, current 425 372
Total current liabilities 22,487 32,857
Liability related to sale of future royalties 6,953 10,365
Deferred license revenue, non-current — 5,999
Contingent consideration 7,600 7,531
Lease liability, non-current 1,343 1,815
Total stockholders’ equity 106,018 136,852
Total liabilities and stockholders’ equity $ 144,401 $ 195,419

UNAUDITED CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS
(in thousands)

Twelve Months Ended December 31,
2023 2022
Net loss $ (72,849 ) $ (69,456 )
Non-cash items 5,146 4,857
Change in deferred license revenue (10,664 ) 22,455
Other changes in working capital (7,569 ) 6,788
Net cash used in operating activities (85,936 ) (35,356 )
Net cash provided by (used in) investing activities 50,773 (74,942 )
Issuance of common shares pursuant to Share Purchase Agreement — 10,973
Issuance of common shares pursuant to the Open Market Sale Agreement 29,852 20,324
Cash provided by other financing activities 795 517
Net cash provided by financing activities 30,647 31,814
Effect of foreign exchange rate changes on cash and cash equivalents 25 (22 )
Decrease in cash and cash equivalents (4,491 ) (78,506 )
Cash and cash equivalents, beginning of period 30,776 109,282
Cash and cash equivalents, end of period 26,285 30,776
Investments in marketable securities 106,002 153,500
Cash, cash equivalents and marketable securities, end of period $ 132,287 $ 184,276

Conference Call and Webcast Today

Arbutus will hold a conference call and webcast today, Thursday, February 29, 2024, at 8:45 AM Eastern Time to provide a corporate update. To dial-in for the conference call by phone, please register using the following link: Registration Link. A live webcast of the conference call can be accessed through the Investors section of Arbutus’ website at www.arbutusbio.com.

An archived webcast will be available on the Arbutus website after the event.

About imdusiran (AB-729)  

Imdusiran is an RNA interference (RNAi) therapeutic specifically designed to reduce all HBV viral proteins and antigens including hepatitis B surface antigen, which is thought to be a key prerequisite to enable reawakening of a patient’s immune system to respond to the virus. Imdusiran targets hepatocytes using Arbutus’ novel covalently conjugated N-Acetylgalactosamine (GalNAc) delivery technology enabling subcutaneous delivery. Clinical data generated thus far has shown single and multiple doses of imdusiran to be generally safe and well-tolerated, while also providing meaningful reductions in hepatitis B surface antigen and hepatitis B DNA. Imdusiran is currently in multiple Phase 2a clinical trials.  

About AB-101  

AB-101 is our oral PD-L1 inhibitor candidate that we believe will allow for controlled checkpoint blockade while minimizing the systemic safety issues typically seen with checkpoint antibody therapies. Immune checkpoints such as PD-1/PD-L1 play an important role in the induction and maintenance of immune tolerance and in T-cell activation. Preclinical data generated thus far indicates that AB-101 mediates re-activation of exhausted HBV-specific T-cells from cHBV patients. We believe AB-101, when used in combination with other approved and investigational agents, could potentially lead to a functional cure in patients chronically infected with HBV. AB-101 is currently being evaluated in a Phase 1a/1b clinical trial.

About HBV  

Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV). HBV can cause chronic infection which leads to a higher risk of death from cirrhosis and liver cancer. Chronic HBV infection represents a significant unmet medical need. The World Health Organization estimates that over 290 million people worldwide suffer from chronic HBV infection, while other estimates indicate that approximately 2.4 million people in the United States suffer from chronic HBV infection. Approximately 820,000 people die every year from complications related to chronic HBV infection despite the availability of effective vaccines and current treatment options.