On April 26, 2023 Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T) products for cancer, reported that it will present updated data from the Phase 1 ALPHA/ALPHA2 trials of ALLO-501/501A at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting June 2 – 6, 2023 in Chicago, Illinois (Press release, Allogene, APR 26, 2023, View Source [SID1234630510]).

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The ALPHA/ALPHA2 trials were designed to assess the safety, tolerability, and preliminary efficacy at increasing dose levels of ALLO-501 and ALLO-501A, allogeneic CAR T cell product candidates that target CD19. In addition to exploring cell doses, these studies evaluated escalating doses of ALLO-647, Allogene’s proprietary lymphodepleting antibody designed to prevent premature rejection of AlloCAR T cells. Allogene is currently enrolling the potentially pivotal Phase 2 ALPHA2 trial of ALLO-501A in large B cell lymphoma (LBCL).

"We are looking forward to sharing updated data from our Phase 1 ALPHA/ALPHA2 trials," said Zachary Roberts, M.D., Ph.D., Executive Vice President, Research & Development and Chief Medical Officer. "Prior updates from the ALPHA/ALPHA2 trials provided clear proof-of-concept for the ability of an allogenic CAR T product candidate to induce deep and durable responses in LBCL, a crucial finding as we seek to establish a new era in CAR T."

Allogene presentation at the 2023 ASCO (Free ASCO Whitepaper) Annual Meeting:

Phase 1 Results with Anti-CD19 Allogeneic CAR T ALLO-501/501A in Relapsed/Refractory Large B Cell Lymphoma (r/r LBCL)

Presenter: Dr. Frederick Locke, M.D., Chair, Department of Blood and Marrow Transplant and Cellular Immunotherapy; program co-leader, Immuno-Oncology, Moffitt Cancer Center
Tampa, Florida
Session Title: Poster Discussion Session – Developmental Therapeutics – Immunotherapy
Abstract: #2517
Poster Board: #359
Poster Session Display Date and Time: June 3, 2023, 8:00AM-11:00AM CT
Poster Discussion Session Date and Time: June 3, 2023, 3:00PM-4:30PM CT

About ALLO-501 and ALLO-501A
ALLO-501 and ALLO-501A are anti-CD19 AlloCAR T investigational products for the treatment of large B cell lymphoma. ALLO-501A, a next-generation anti-CD19 AlloCAR T, eliminates the rituximab recognition domains in ALLO-501, which could allow for use in a broader patient population, including NHL patients with recent rituximab exposure. This product candidate is currently being studied in an ongoing Phase 2 trial. In June 2022, the U.S. Food and Drug Administration granted Regenerative Medicine Advanced Therapy (RMAT) designation to ALLO-501A in r/r LBCL.

On April 26, 2023 Alkermes plc (Nasdaq: ALKS) reported its financial results for the first quarter of 2023 (Press release, Alkermes, APR 26, 2023, View Source [SID1234630509]).

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"During the first quarter we made continued progress across our portfolio, including strong commercial execution driving growth for our proprietary products – LYBALVI, VIVITROL and ARISTADA – and important progress in the development of ALKS 2680, our orexin 2 receptor agonist, which is now poised to enter a phase 1b proof-of-concept study in patients with narcolepsy and idiopathic hypersomnia, with data expected later this year," said Richard Pops, Chief Executive Officer of Alkermes. "In addition, we made significant operational and strategic advances in the planned separation of our oncology business, which remains on track for completion in the second half of this year. We remain sharply focused on executing our strategic priorities to create significant value for shareholders."

"Our strong first quarter financial results were driven by 25% growth year-over-year in proprietary product net sales and continued focus on disciplined management of our cost structure," commented Iain Brown, Chief Financial Officer of Alkermes. "Today, we are reiterating our financial expectations for 2023 and believe we are in a strong financial position to continue to execute our strategic priorities, including further driving the launch of LYBALVI, advancing our orexin 2 receptor agonist clinical development program and completing the planned separation of the oncology business later this year."

Quarter Ended March 31, 2023 Financial Results

Revenues

– Total revenues for the quarter were $287.6 million, compared to $278.5 million for the same period in the prior year.

– Net sales of proprietary products for the quarter increased approximately 25% to $214.7 million, compared to $171.3 million for the same period in the prior year.

Net sales of VIVITROL were $96.7 million, compared to $84.9 million for the same period in the prior year, representing an increase of approximately 14%.
Net sales of ARISTADAi were $80.1 million, compared to $72.5 million for the same period in the prior year, representing an increase of approximately 10%.
Net sales of LYBALVI were $38.0 million, compared to $13.9 million for the same period in the prior year, representing an increase of approximately 173%.
– Manufacturing and royalty revenues for the quarter were $72.9 million, compared to $105.2 million for the same period in the prior year.

Royalty revenues from INVEGA SUSTENNA/XEPLION, INVEGA TRINZA/TREVICTA and INVEGA HAFYERA/BYANNLI (the long-acting INVEGA products) for the quarter were $13.6 million, compared to $37.1 million for the same period in the prior year. This decrease was driven primarily by Janssen Pharmaceutica N.V.’s (Janssen), a subsidiary of Johnson & Johnson, partial termination of the license agreement related to sales of the long-acting INVEGA products in the United States (U.S.), effective Feb. 2, 2022.
Manufacturing and royalty revenues from VUMERITY for the quarter were $28.9 million, compared to $30.6 million for the same period in the prior year.
Costs and Expenses

– Total operating expenses for the quarter were $335.1 million, compared to $305.1 million for the same period in the prior year. The increase was driven primarily by investment in the launch of LYBALVI and expenses associated with the planned separation of the oncology business.

Cost of Goods Manufactured and Sold was $58.2 million, compared to $55.2 million for the same period in the prior year.
Research and Development (R&D) expenses were $93.6 million, compared to $96.0 million for the same period in the prior year.
Selling, General and Administrative (SG&A) expenses were $174.5 million, compared to $145.1 million for the same period in the prior year, primarily reflecting increased investment to support the launch of LYBALVI.
Profitability

– Net loss according to generally accepted accounting principles in the U.S. (GAAP) was $41.8 million for the quarter, or a basic and diluted GAAP loss per share of $0.25. This compared to GAAP net loss of $35.9 million, or a basic and diluted GAAP loss per share of $0.22, for the same period in the prior year.

– Non-GAAP net income was $2.4 million for the quarter, or a non-GAAP basic and diluted earnings per share of $0.01. This compared to non-GAAP net income of $19.6 million, or a non-GAAP basic and diluted earnings per share of $0.12, for the same period in the prior year.

Balance Sheet

– At March 31, 2023, the company recorded cash, cash equivalents and total investments of $692.5 million, compared to $740.1 million at Dec. 31, 2022. The company’s total debt outstanding as of March 31, 2023 was $292.6 million.

Financial Expectations for 2023

Alkermes reiterates its financial expectations for 2023, as set forth in its press release dated Feb. 16, 2023.

Separation of Oncology Business

Alkermes continues to make meaningful progress on the previously announced planned separation of the company’s oncology business. The separation would allow Alkermes to maintain its focus on researching, developing and commercializing therapies for people living with complex neurological conditions and is expected to accelerate and enhance the profitability of the remaining neuroscience business.

– As previously announced, in April, Alkermes submitted a confidential draft Form 10 registration statement to the United States Securities and Exchange Commission (SEC) in connection with the planned separation of its oncology business into an independent, publicly-traded company. Upon completion of the planned separation, the new company would be known as Mural Oncology plc.

– Alkermes continues to expect to complete the separation in the second half of 2023, subject to various customary conditions, including final approval from Alkermes’ board of directors.

Recent Events

Corporate

– In April 2023, the company received a second favorable interim award (the Second Interim Award) from the arbitral tribunal (the Tribunal) in the company’s arbitration proceedings with Janssen in respect of Janssen’s partial termination in the U.S. of two license agreements with the company. The Second Interim Award, which builds on the first interim award that was issued in December 2022, provides that back royalties related to 2022 of approximately $194 million (inclusive of interest) are due to the company under the two agreements, and that a separate Know-How Royalty (as defined in the applicable license agreement) term applies for each of INVEGA SUSTENNA, INVEGA TRINZA and INVEGA HAFYERA.

Neuroscience

– In February 2023, the company initiated a multiple ascending dose cohort in the phase 1 study of its ALKS 2680 orexin 2 receptor agonist, which is in clinical development for the treatment of narcolepsy and other hypersomnia conditions.

– In March 2023, the company announced the publication of results from its phase 3 ENLIGHTEN-Early study of LYBALVI in the peer-reviewed publication, the Journal of Clinical Psychiatry. ENLIGHTEN-Early evaluated the effect of LYBALVI compared to olanzapine on body weight in young adult patients (ages 16 to 39; mean age: 26 years) with schizophrenia, schizophreniform disorder or bipolar I disorder who were early in their illness.

Conference Call

Alkermes will host a conference call and webcast presentation with accompanying slides at 8:00 a.m. ET (1:00 p.m. BST) on Wednesday, April 26, 2023, to discuss these financial results and provide an update on the company. The webcast may be accessed on the Investors section of Alkermes’ website at www.alkermes.com. The conference call may be accessed by dialing +1 877 407 2988 for U.S. callers and +1 201 389 0923 for international callers. In addition, a replay of the conference call may be accessed by visiting Alkermes’ website.

On April 25, 2023 Alentis Therapeutics ("Alentis"), the clinical-stage biotechnology company developing breakthrough treatments for organ fibrosis and CLDN1+ tumors, reported results from the multiple-ascending dose (MAD) part of its first-in-human Phase 1 clinical study of ALE.F02 targeting Claudin-1 (CLDN1) (Press release, Alentis Therapeutics, APR 26, 2023, View Source [SID1234630480]).

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The trial enrolled 24 subjects: 18 received the active drug and six received placebo across three dose levels. Participants were dosed every two weeks.

Dr. Luigi Manenti, Chief Medical Officer at Alentis said: "This study is the first to target CLDN1 in humans. ALE.F02 showed good safety and tolerability at multiple dose levels. There were no serious events and no dose delays or reductions." Dr. Manenti added that the pharmacokinetics data confirmed the desired exposures, specifically, that the concentrations required for extracellular remodeling were achieved.

Speaking to the pharmacodynamics, Dr. Manenti said, "We not only confirmed the evidence of on-target biological activity that we witnessed in our single-ascending dose (SAD) study last June, but we also saw this enriched in the MAD part of the trial."

"We achieved what we set out to do in both the SAD and MAD studies," said Dr. Roberto Iacone, CEO of Alentis Therapeutics. "The successful conclusion of this trial validates that Claudin-1 is a safe target. With ALE.F02 being safe and well tolerated, Alentis can progress platform and indication expansion. This puts us in a strong position as we advance to the next phase of development starting with first-in-patient liver and renal studies this year."

On April 16, 2023 Chimeric Therapeutics (ASX:CHM, "Chimeric" or the "Company"), the only ASX-listed clinical
stage cell therapy company, reported that it has received ethics approval for the initiation of a multi-site Phase 1B clinical trial of CHM 1101 in patients with recurrent and/ or progressive glioblastoma multiforme (GBM) (Press release, Chimeric Therapeutics, APR 26, 2023, View Source [SID1234630478]). This new chapter in the development of CHM 1101 will see Chimeric leading a two-part Phase 1B clinical study enrolling patients with recurrent and/ or progressive GBM at multiple clinical trial sites.

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Part A of the trial will treat 3-6 patients, completing the Phase 1 CHM 1101 dose escalation/confirmation study that was initiated at City of Hope Cancer Centre. At the end of 2023, an assessment of clinical safety and efficacy data from the Phase 1 dose escalation/ confirmation cohort will be undertaken. Should the results of that assessment
support further development, Part B of the trial design would be initiated.

Part B of the trial is a dose expansion cohort designed to enroll 12-26 patients with recurrent and/ or progressive GBM using the recommended Phase 2 dosing plan and assessing for efficacy and safety.

Upon successful completion of the Part B dose expansion cohort, a registration trial will be initiated in alignment with regulatory feedback.

"Expanding our clinical program to additional sites is critical to our mission to deliver our medicines to the patients who need them," said Dr Jason Litten, Chief Medical Officer of Chimeric Therapeutics. "The two-part trial design also ensures that we are positioned to move rapidly into the dose expansion cohort upon a positive clinical assessment of the Phase 1 data at the end of 2023."

Additional details on the CHM Phase 1B trial design and objectives are being presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting as part of the Central Nervous System Tumors section on June 3, 2023.

About CHM 1101:

CHM 1101 (CLTX CAR T) is a first in class CAR T therapy that has the potential to address the high unmet medical need of patients with recurrent or progressive glioblastoma, patients who have a poor prognosis, with limited treatment options and a median survival of less than 1 year (Gallego. Curr Oncol, 2015).

CHM 1101 cells uniquely utilize chlorotoxin (CLTX), a 36-amino acid peptide derived from deathstalker scorpion venom, as the tumour-targeting component of the chimeric antigen For personal use only receptor (CAR).

In preclinical models, CHM 1101 CAR T cells have been shown to bind more broadly and specifically to GBM cells than other targeting domains like EGFR, HER-2 or IL-13. CHM 1101 cells also demonstrated potent antitumor activity against glioblastoma while not exhibiting any off-tumor recognition of normal human cells and tissues, indicating a potentially optimal safety and efficacy profile.

CHM 1101 is currently being studied in an ongoing phase 1A clinical trial in recurrent / progressive glioblastoma at City of Hope Cancer Centre in California. Outcomes from the initial two dose levels of the Phase 1A trial have been previously presented and demonstrated patient safety with a disease stability rate of approximately 70%.

On April 25, 2023 Incurix reported preclinical results of MYC (C-Myc) inhibitor ‘ICX-101’ at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (ACCR 2023) (Press release, Incurix, APR 25, 2023, View Source;idx=92&page=1&code=news [SID1234643577]).

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ICX-101 is a substance that Incurix licensed (L/I) from the National Cancer Center and the Korea Research Institute of Chemical Technology in 2023, and Incurix CEO Jeong Kyeong-chae led the drug development. Incurix is ​​developing ICX-101 in the preclinical stage.

Choi Won-young, a senior researcher at the National Cancer Center, presented the results of in vitro research on ICX-101 at the ACCR held in Orlando, USA on the 18th (local time).

ICX-101 is a MYC inhibitor, a small molecule compound that prevents MYC from binding to DNA by forming a dimer with MAX. MYC is a cancer-causing transcription factor and is known to play an important role in cell division and cell survival along with MAX.

In this study, the National Cancer Center evaluated the drug responsiveness of ICX-101 in lung cancer patient-derived cancer cells (PDC). As a result of the study, it was confirmed that cancer cells with higher MYC mRNA levels were more responsive to ICX-101. In addition, MYC expression was found to be high in lung cancer patient-derived cells, especially small cell lung cancer (SCLC).

Specifically, the National Cancer Center collected cancer tissues from 82 lung cancer patients and classified cancer cells according to histological type. Accordingly, a total of 100 samples were collected, including 82 adenocarcinoma, 10 squamous cell carcinoma, 4 non-small cell lung cancer (NSCLC), and 4 SCLC. As a result of checking the expression level of MYC in these samples, the expression level of MYC was highest in SCLC samples and was found to be significantly higher than that in NSCLC (p=0.004).

Next, the degree of response to ICX-101 was evaluated when the samples were classified into three groups according to the level of MYC expression: top 25%, middle 50%, and bottom 25%. As a result, it was found that samples in the top 25% of MYC expression levels responded more sensitively to ICX-101 than samples in the bottom 25%. It was confirmed that sensitivity to ICX-101 increases as the level of MYC expression increases.

Senior Researcher Choi said, "Looking at the overall survival data of patients from whom PDC was collected, it was confirmed that patients with high MYC expression had a poorer prognosis than patients with low MYC expression. Based on this data, from a long-term perspective, "It is expected that ICX-101 can induce a good response in patients with poor prognosis due to high MYC expression," he said.

Additionally, Senior Researcher Choi explained, "Because SCLC samples were found to have higher MYC expression than NSCLC, we view this as a promising indication for ICX-101."